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    Clinical Trial Results:
    A Phase II/III, Randomised, Multicentre Study of MOR00208 with Bendamustine versus Rituximab with Bendamustine in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL) Who Are Not Eligible for High-Dose Chemotherapy (HDC) and Autologous Stem-Cell Transplantation (ASCT)

    Summary
    EudraCT number
    		 2014-004689-11
    Trial protocol
    		 HU   DE   FI   PT   FR   AT   CZ   ES   RO   GB   HR   IT  
    Global end of trial date
    21 Jun 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Jun 2025
    First version publication date
    07 Jun 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MOR208C204
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Abbreviation: B-MIND
    Sponsors
    Sponsor organisation name
    Incyte Corporation
    Sponsor organisation address
    1801 Augustine Cutoff, Wilmington, United States, 19803
    Public contact
    Study Director, Incyte Corporation, 1 8554633463, medinfo@incyte.com
    Scientific contact
    Study Director, Incyte Corporation, 1 8554633463, medinfo@incyte.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    21 Jun 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Jun 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the efficacy of a combination of tafasitamab with bendamustine versus a combination of rituximab with bendamustine in terms of progression-free survival (PFS) in adult participants with relapsed or refractory diffuse large B-cell lymphoma (R-R DLBCL)
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles of Good Clinical Practice, according to the International Council for Harmonisation Guidelines
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Aug 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 44
    Country: Number of subjects enrolled
    Austria: 5
    Country: Number of subjects enrolled
    Canada: 17
    Country: Number of subjects enrolled
    Croatia: 7
    Country: Number of subjects enrolled
    Czechia: 22
    Country: Number of subjects enrolled
    Finland: 3
    Country: Number of subjects enrolled
    France: 13
    Country: Number of subjects enrolled
    Germany: 27
    Country: Number of subjects enrolled
    Hungary: 13
    Country: Number of subjects enrolled
    Israel: 12
    Country: Number of subjects enrolled
    Italy: 60
    Country: Number of subjects enrolled
    Korea, Republic of: 73
    Country: Number of subjects enrolled
    New Zealand: 9
    Country: Number of subjects enrolled
    Poland: 16
    Country: Number of subjects enrolled
    Portugal: 19
    Country: Number of subjects enrolled
    Romania: 5
    Country: Number of subjects enrolled
    Serbia: 31
    Country: Number of subjects enrolled
    Singapore: 5
    Country: Number of subjects enrolled
    Spain: 18
    Country: Number of subjects enrolled
    Taiwan: 6
    Country: Number of subjects enrolled
    Türkiye: 25
    Country: Number of subjects enrolled
    United Kingdom: 11
    Country: Number of subjects enrolled
    United States: 12
    Worldwide total number of subjects
    453
    EEA total number of subjects
    208
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    85
    From 65 to 84 years
    354
    85 years and over
    14

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 This study was conducted at 138 study centers in: Australia, Austria, Canada, Croatia, Czech Republic, Finland, France, Germany, Hungary, Israel, Italy, New Zealand, Poland, Portugal, Romania, Serbia, South Korea, Spain, Singapore, Taiwan, Turkey, the United Kingdom, and the United States of America.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Tafasitamab + bendamustine
    Arm description
    		 Participants received intravenous (IV) tafasitamab 12.0 milligrams per kilogram (mg/kg) in combination with IV bendamustine 90 mg/meters squared (m^2) in 28-day cycles for a maximum of 6 cycles. During Cycles 1 to 3, participants received tafastiamab on Days 1, 8, 15, and 22, plus a loading dose on Day 4 of Cycle 1. Participants received bendamustine on either Days 2 and 3 or Days 1 and 2 of Cycles 1 to 6. Participants with an ongoing response of at least partial response at the end of Cycle 6, as per local assessment, continued tafasitamab or rituximab monotherapy per initially allocated treatment until disease progression. Treatment was stopped due to disease progression, unacceptable toxicity, death, or discontinuation for any other reason, whichever came first.
    Arm type
    		 Experimental

    Investigational medicinal product name
    bendamustine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    dosage level = 90 mg/m^2

    Investigational medicinal product name
    Tafasitamab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    lyophilisate for solution for infusion; dosage level = 12.0 mg/kg

    Arm title
    		 Rituximab + bendamustine
    Arm description
    		 Participants received IV rituximab 375 mg/m^2 in combination with IV bendamustine 90 mg/m^2 in 28-day cycles for a maximum of 6 cycles. Participants received rituximab on Day 1 of each cycle until disease progression. Participants received bendamustine on either Days 2 and 3 or Days 1 and 2 of Cycles 1 to 6. Participants with an ongoing response of at least partial response at the end of Cycle 6, as per local assessment, continued tafasitamab or rituximab monotherapy per initially allocated treatment until disease progression. Treatment was stopped due to disease progression, unacceptable toxicity, death, or discontinuation for any other reason, whichever came first.
    Arm type
    		 Experimental

    Investigational medicinal product name
    bendamustine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    dosage level = 90 mg/m^2

    Investigational medicinal product name
    rituximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    dosage level = 375 mg/m^2

    Number of subjects in period 1
    		Tafasitamab + bendamustine Rituximab + bendamustine
    Started
    226
    227
    Completed
    0
    0
    Not completed
    226
    227
         Noncompliance with Study Drug
    2
    -
         Physician decision
    1
    7
         Consent withdrawn by subject
    26
    25
         Completed Maximum per Protocol Treatment Period
    1
    -
         Adverse event, non-fatal
    12
    3
         Death
    123
    123
         Progressive Disease
    24
    27
         Captured as "Other" in Database
    29
    34
         Lost to follow-up
    6
    7
         Tested Positive for Coronavirus SARS-CoV-2
    2
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Tafasitamab + bendamustine
    Reporting group description
    		 Participants received intravenous (IV) tafasitamab 12.0 milligrams per kilogram (mg/kg) in combination with IV bendamustine 90 mg/meters squared (m^2) in 28-day cycles for a maximum of 6 cycles. During Cycles 1 to 3, participants received tafastiamab on Days 1, 8, 15, and 22, plus a loading dose on Day 4 of Cycle 1. Participants received bendamustine on either Days 2 and 3 or Days 1 and 2 of Cycles 1 to 6. Participants with an ongoing response of at least partial response at the end of Cycle 6, as per local assessment, continued tafasitamab or rituximab monotherapy per initially allocated treatment until disease progression. Treatment was stopped due to disease progression, unacceptable toxicity, death, or discontinuation for any other reason, whichever came first.

    Reporting group title
    Rituximab + bendamustine
    Reporting group description
    		 Participants received IV rituximab 375 mg/m^2 in combination with IV bendamustine 90 mg/m^2 in 28-day cycles for a maximum of 6 cycles. Participants received rituximab on Day 1 of each cycle until disease progression. Participants received bendamustine on either Days 2 and 3 or Days 1 and 2 of Cycles 1 to 6. Participants with an ongoing response of at least partial response at the end of Cycle 6, as per local assessment, continued tafasitamab or rituximab monotherapy per initially allocated treatment until disease progression. Treatment was stopped due to disease progression, unacceptable toxicity, death, or discontinuation for any other reason, whichever came first.

    Reporting group values
    		 Tafasitamab + bendamustine Rituximab + bendamustine Total
    Number of subjects
    		 226 227 453
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 42 42 84
        From 65-84 years
    		 176 178 354
        85 years and over
    		 8 7 15
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 70.9 ( 10.36 ) 70.8 ( 9.92 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 96 96 192
        Male
    		 130 131 261
    Race/Ethnicity, Customized
    Units: Subjects
        Black or African American
    		 1 0 1
        American Indian or Alaskan Native
    		 1 0 1
        Asian
    		 41 45 86
        Native Hawaiian or Other Pacific Islander
    		 0 1 1
        White
    		 172 171 343
        Not Applicable in Enrolled Country
    		 8 4 12
        Captured as "Other" in Database
    		 2 2 4
        Iraqi
    		 1 0 1
        European
    		 0 2 2
        Eurasian
    		 0 1 1
        Captured as "Hispanic" in Database
    		 0 1 1

    End points

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    End points reporting groups
    Reporting group title
    Tafasitamab + bendamustine
    Reporting group description
    		 Participants received intravenous (IV) tafasitamab 12.0 milligrams per kilogram (mg/kg) in combination with IV bendamustine 90 mg/meters squared (m^2) in 28-day cycles for a maximum of 6 cycles. During Cycles 1 to 3, participants received tafastiamab on Days 1, 8, 15, and 22, plus a loading dose on Day 4 of Cycle 1. Participants received bendamustine on either Days 2 and 3 or Days 1 and 2 of Cycles 1 to 6. Participants with an ongoing response of at least partial response at the end of Cycle 6, as per local assessment, continued tafasitamab or rituximab monotherapy per initially allocated treatment until disease progression. Treatment was stopped due to disease progression, unacceptable toxicity, death, or discontinuation for any other reason, whichever came first.

    Reporting group title
    Rituximab + bendamustine
    Reporting group description
    		 Participants received IV rituximab 375 mg/m^2 in combination with IV bendamustine 90 mg/m^2 in 28-day cycles for a maximum of 6 cycles. Participants received rituximab on Day 1 of each cycle until disease progression. Participants received bendamustine on either Days 2 and 3 or Days 1 and 2 of Cycles 1 to 6. Participants with an ongoing response of at least partial response at the end of Cycle 6, as per local assessment, continued tafasitamab or rituximab monotherapy per initially allocated treatment until disease progression. Treatment was stopped due to disease progression, unacceptable toxicity, death, or discontinuation for any other reason, whichever came first.

    Primary: Kaplan-Meier Estimate of Progression-Free Survival by Independent Radiology/Clinical Review Committee Assessment in the Overall Population

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    End point title
    		 Kaplan-Meier Estimate of Progression-Free Survival by Independent Radiology/Clinical Review Committee Assessment in the Overall Population
    End point description
    Progression-free survival was defined as the time from randomization to tumor progression or death from any cause. The Full Analysis Set was comprised of all participants who were randomized to either treatment arm. Participants were analyzed according to the treatment and stratification factors they were assigned to during the randomization procedure. 95% confidence intervals (CIs) (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley.
    End point type
    Primary
    End point timeframe
    up to 41.4 months
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    226 [1]
    227 [2]
    Units: months
        median (confidence interval 95%)
    7.10 (5.800 to 8.500)
    8.30 (5.600 to 11.500)
    Notes
    [1] - Full Analysis Set
    [2] - Full Analysis Set
    Statistical analysis title
    		 PFS: Overall Population
    Comparison groups
    Tafasitamab + bendamustine v Rituximab + bendamustine
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.468
    Method
    		 Inverse normal test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.837
         upper limit
    		 1.351

    Primary: Kaplan-Meier Estimate of Progression-Free Survival by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer (NK) Cell Count-Low Subgroup

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    End point title
    		 Kaplan-Meier Estimate of Progression-Free Survival by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer (NK) Cell Count-Low Subgroup
    End point description
    Progression-free survival was defined as the time from randomization to tumor progression or death from any cause. The Natural Killer Cell Count-Low Full Analysis Set (NK CC-Low FAS) was comprised of all participants in the FAS with ≤100 NK cells/µL at Baseline. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley.
    End point type
    Primary
    End point timeframe
    up to 46.5 months
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    88 [3]
    74 [4]
    Units: months
        median (confidence interval 95%)
    5.60 (4.400 to 8.600)
    5.60 (3.600 to 10.000)
    Notes
    [3] - Natural Killer Cell Count-Low Full Analysis Set
    [4] - Natural Killer Cell Count-Low Full Analysis Set
    Statistical analysis title
    		 PFS: Natural Killer Cell Count-Low Subgroup
    Comparison groups
    Tafasitamab + bendamustine v Rituximab + bendamustine
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.568
    Method
    		 Inverse normal test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.586
         upper limit
    		 1.33

    Secondary: Kaplan-Meier Estimate of Duration of Response by Independent Radiology/Clinical Review Committee Assessment in the Overall Population

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    End point title
    		 Kaplan-Meier Estimate of Duration of Response by Independent Radiology/Clinical Review Committee Assessment in the Overall Population
    End point description
    Duration of response was defined as the elapsed time (in months) between the date of the first documented response (CR or PR) and the following date of an event defined as the first documented progression (any new lesion or an increase by ≥50% of previously involved sites from nadir) or death. Per International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley.
    End point type
    Secondary
    End point timeframe
    up to 40.2 months
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    148 [5]
    140 [6]
    Units: months
        median (confidence interval 95%)
    7.40 (5.800 to 12.100)
    12.10 (10.000 to 23.300)
    Notes
    [5] - Full Analysis Set. Only participants with CR or PR were analyzed.
    [6] - Full Analysis Set. Only participants with CR or PR were analyzed.
    Statistical analysis title
    		 DOR: Overall Population
    Comparison groups
    Tafasitamab + bendamustine v Rituximab + bendamustine
    Number of subjects included in analysis
    288
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.938
         upper limit
    		 1.745

    Secondary: Best ORR by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup

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    End point title
    		 Best ORR by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup
    End point description
    Best ORR was defined as the percentage of patients with CR or PR based on the best response achieved at any time during the study. Per International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites. A 2-sided 95% Clopper-Pearson exact method based on binomial distribution was used.
    End point type
    Secondary
    End point timeframe
    up to 77 months
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    88 [7]
    74 [8]
    Units: percentage of participants
        number (confidence interval 95%)
    64.8 (53.86 to 74.66)
    59.5 (47.41 to 70.73)
    Notes
    [7] - Natural Killer Cell Count-Low Full Analysis Set
    [8] - Natural Killer Cell Count-Low Full Analysis Set
    Statistical analysis title
    		 ORR: Natural Killer Cell Count-Low Subgroup
    Comparison groups
    Tafasitamab + bendamustine v Rituximab + bendamustine
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.778
         upper limit
    		 3.041

    Secondary: Best Objective Response Rate (ORR) by Independent Radiology/Clinical Review Committee Assessment in the Overall Population

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    End point title
    		 Best Objective Response Rate (ORR) by Independent Radiology/Clinical Review Committee Assessment in the Overall Population
    End point description
    Best ORR was defined as the percentage of patients with complete response (CR) or partial response (PR) based on the best response achieved at any time during the study. Per International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites. A 2-sided 95% Clopper-Pearson exact method based on binomial distribution was used.
    End point type
    Secondary
    End point timeframe
    up to 77 months
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    226 [9]
    227 [10]
    Units: percentage of participants
        number (confidence interval 95%)
    65.5 (58.90 to 71.67)
    61.7 (55.01 to 68.03)
    Notes
    [9] - Full Analysis Set
    [10] - Full Analysis Set
    Statistical analysis title
    		 ORR: Overall Population
    Comparison groups
    Tafasitamab + bendamustine v Rituximab + bendamustine
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.812
         upper limit
    		 1.779

    Secondary: Kaplan-Meier Estimate of Overall Survival in the Overall Population

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    End point title
    		 Kaplan-Meier Estimate of Overall Survival in the Overall Population
    End point description
    Overall survival was defined as the time (in months) from randomization until death from any cause. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley.
    End point type
    Secondary
    End point timeframe
    up to 50.0 months
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    226 [11]
    227 [12]
    Units: months
        median (confidence interval 95%)
    14.60 (11.600 to 23.400)
    20.20 (13.400 to 24.300)
    Notes
    [11] - Full Analysis Set
    [12] - Full Analysis Set
    Statistical analysis title
    		 Overall Survival: Overall Population
    Comparison groups
    Tafasitamab + bendamustine v Rituximab + bendamustine
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.875
         upper limit
    		 1.452

    Secondary: Kaplan-Meier Estimate of Duration of Response by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup

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    End point title
    		 Kaplan-Meier Estimate of Duration of Response by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup
    End point description
    Duration of response was defined as the elapsed time (in months) between the date of the first documented response (CR or PR) and the following date of an event defined as the first documented progression (any new lesion or an increase by ≥50% of previously involved sites from nadir) or death. Per International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley.
    End point type
    Secondary
    End point timeframe
    up to 44.7 months
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    57 [13]
    44 [14]
    Units: months
        median (confidence interval 95%)
    6.70 (3.700 to 12.700)
    10.30 (4.900 to 37.500)
    Notes
    [13] - Natural Killer Cell Count-Low Full Analysis Set. Only participants with CR or PR were analyzed.
    [14] - Natural Killer Cell Count-Low Full Analysis Set. Only participants with CR or PR were analyzed.
    Statistical analysis title
    		 DOR: Natural Killer Cell Count-Low Subgroup
    Comparison groups
    Tafasitamab + bendamustine v Rituximab + bendamustine
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.673
         upper limit
    		 2.035

    Secondary: Kaplan-Meier Estimate of Overall Survival in the Natural Killer Cell Count-Low Subgroup

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    End point title
    		 Kaplan-Meier Estimate of Overall Survival in the Natural Killer Cell Count-Low Subgroup
    End point description
    Overall survival (OS) was defined as the time (in months) from randomization until death from any cause. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley.
    End point type
    Secondary
    End point timeframe
    up to 50.6 months
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    88 [15]
    74 [16]
    Units: months
        median (confidence interval 95%)
    10.60 (8.300 to 19.700)
    12.50 (8.300 to 32.300)
    Notes
    [15] - Natural Killer Cell Count-Low Full Analysis Set
    [16] - Natural Killer Cell Count-Low Full Analysis Set
    Statistical analysis title
    		 OS: Natural Killer Cell Count-Low Subgroup
    Comparison groups
    Tafasitamab + bendamustine v Rituximab + bendamustine
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.682
         upper limit
    		 1.626

    Secondary: Disease Control Rate (DCR) by Independent Radiology/Clinical Review Committee Assessment in the Overall Population

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    End point title
    		 Disease Control Rate (DCR) by Independent Radiology/Clinical Review Committee Assessment in the Overall Population
    End point description
    DCR was defined as the percentage of participants with a CR, PR, or stable disease (SD) based on the best response achieved at any time during the study. Per the International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites; SD: failure to attain CR/PR or progressive disease (PD; any new lesion or an increase by ≥50% of previously involved sites from nadir). A 2-sided 95% Clopper-Pearson exact method based on binomial distribution was used.
    End point type
    Secondary
    End point timeframe
    up to 77 months
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    226 [17]
    227 [18]
    Units: percentage of participants
        number (confidence interval 95%)
    76.1 (70.00 to 81.51)
    71.8 (65.47 to 77.56)
    Notes
    [17] - Full Analysis Set
    [18] - Full Analysis Set
    Statistical analysis title
    		 DCR: Overall Population
    Comparison groups
    Tafasitamab + bendamustine v Rituximab + bendamustine
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.829
         upper limit
    		 1.985

    Secondary: DCR by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup

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    End point title
    		 DCR by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup
    End point description
    DCR was defined as the percentage of participants with a CR, PR, or SD based on the best response achieved at any time during the study. Per the International Working Group response criteria: CR: the disappearance of all evidence of disease; PR: regression of measurable disease and no new sites; SD: failure to attain CR/PR or PD (any new lesion or an increase by ≥50% of previously involved sites from nadir). A 2-sided 95% Clopper-Pearson exact method based on binomial distribution was used.
    End point type
    Secondary
    End point timeframe
    up to 77 months
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    88 [19]
    74 [20]
    Units: percentage of participants
        number (confidence interval 95%)
    75.0 (64.63 to 83.62)
    70.3 (58.52 to 80.34)
    Notes
    [19] - Natural Killer Cell Count-Low Full Analysis Set
    [20] - Natural Killer Cell Count-Low Full Analysis Set
    Statistical analysis title
    		 DCR: Natural Killer Cell Count-Low Subgroup
    Comparison groups
    Tafasitamab + bendamustine v Rituximab + bendamustine
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.755
         upper limit
    		 3.457

    Secondary: Kaplan-Meier Estimate of Time to Progression by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup

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    End point title
    		 Kaplan-Meier Estimate of Time to Progression by Independent Radiology/Clinical Review Committee Assessment in the Natural Killer Cell Count-Low Subgroup
    End point description
    Time to progression was defined as the time (in months) from randomization until documented diffuse large B-call lymphoma (DLBCL) progression or death as a result of lymphoma. Death from other causes than lymphoma was not considered in relation to the TTP evaluation. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley.
    End point type
    Secondary
    End point timeframe
    up to 40.6 months
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    50 [21]
    36 [22]
    Units: months
        median (confidence interval 95%)
    8.00 (5.400 to 9.200)
    10.00 (3.800 to 39.400)
    Notes
    [21] - NK CC-Low FAS. Only participants with progression/death as a result of lymphoma were analyzed.
    [22] - NK CC-Low FAS. Only participants with progression/death as a result of lymphoma were analyzed.
    Statistical analysis title
    		 TTP: Natural Killer Cell Count-Low Subgroup
    Comparison groups
    Tafasitamab + bendamustine v Rituximab + bendamustine
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.633
         upper limit
    		 1.595

    Secondary: Kaplan-Meier Estimate of Time to Progression (TTP) by Independent Radiology/Clinical Review Committee Assessment in the Overall Population

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    End point title
    		 Kaplan-Meier Estimate of Time to Progression (TTP) by Independent Radiology/Clinical Review Committee Assessment in the Overall Population
    End point description
    Time to progression was defined as the time (in months) from randomization until documented diffuse large B-call lymphoma (DLBCL) progression or death as a result of lymphoma. Death from other causes than lymphoma was not considered in relation to the TTP evaluation. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley.
    End point type
    Secondary
    End point timeframe
    up to 25.8 months
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    117 [23]
    111 [24]
    Units: months
        median (confidence interval 95%)
    8.20 (6.200 to 9.300)
    11.10 (8.100 to 18.300)
    Notes
    [23] - Full Analysis Set. Only participants with progression/death as a result of lymphoma were analyzed.
    [24] - Full Analysis Set. Only participants with progression/death as a result of lymphoma were analyzed.
    Statistical analysis title
    		 TTP: Overall Population
    Comparison groups
    Tafasitamab + bendamustine v Rituximab + bendamustine
    Number of subjects included in analysis
    228
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.831
         upper limit
    		 1.416

    Secondary: Kaplan-Meier Estimate of Time to Next Treatment in the Natural Killer Cell Count-Low Subgroup

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    End point title
    		 Kaplan-Meier Estimate of Time to Next Treatment in the Natural Killer Cell Count-Low Subgroup
    End point description
    Time to next treatment was defined as the time (in months) from randomization to the institution of the next anti-neoplastic therapy (for any reason including disease progression, treatment toxicity, and participant preference) or death due to any cause, whatever came first. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley.
    End point type
    Secondary
    End point timeframe
    up to 70.1 months
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    88 [25]
    74 [26]
    Units: months
        median (confidence interval 95%)
    7.20 (5.800 to 9.500)
    6.30 (4.300 to 9.000)
    Notes
    [25] - Natural Killer Cell Count-Low Full Analysis Set
    [26] - Natural Killer Cell Count-Low Full Analysis Set
    Statistical analysis title
    		 TTNT: Natural Killer Cell Count-Low Subgroup
    Comparison groups
    Tafasitamab + bendamustine v Rituximab + bendamustine
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.57
         upper limit
    		 1.22

    Secondary: Kaplan-Meier Estimate of Time to Next Treatment (TTNT) in the Overall Population

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    End point title
    		 Kaplan-Meier Estimate of Time to Next Treatment (TTNT) in the Overall Population
    End point description
    Time to next treatment was defined as the time (in months) from randomization to the institution of the next anti-neoplastic therapy (for any reason including disease progression, treatment toxicity, and participant preference) or death due to any cause, whatever came first. 95% CIs (Greenwood formula) for the median and the 25th and 75th percentiles were calculated using the method of Brookmeyer and Crowley.
    End point type
    Secondary
    End point timeframe
    up to 59.4 months
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    226 [27]
    227 [28]
    Units: months
        median (confidence interval 95%)
    8.80 (7.500 to 10.900)
    8.70 (6.800 to 11.500)
    Notes
    [27] - Full Analysis Set
    [28] - Full Analysis Set
    Statistical analysis title
    		 TTNT: Overall Population
    Comparison groups
    Tafasitamab + bendamustine v Rituximab + bendamustine
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.794
         upper limit
    		 1.244

    Secondary: Number of participants with any treatment-emergent adverse event (TEAE)

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    End point title
    		 Number of participants with any treatment-emergent adverse event (TEAE)
    End point description
    An adverse event was defined as any untoward medical occurrence in a participant administered a medicinal product, which did not necessarily have a causal relationship to this treatment. An AE could therefore have been any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it was considered related to that study drug. TEAEs were defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug. The Safety Analysis Set was comprised of all participants who received at least one dose of tafasitamab, bendamustine, or rituximab. Analyses were based on the actual treatment received.
    End point type
    Secondary
    End point timeframe
    up to 77 months
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    219 [29]
    225 [30]
    Units: percentage of participants
    215
    215
    Notes
    [29] - Safety Analysis Set
    [30] - Safety Analysis Set
    No statistical analyses for this end point

    Secondary: Number of participants with any Grade 3 or higher TEAE

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    End point title
    		 Number of participants with any Grade 3 or higher TEAE
    End point description
    AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (or higher). Grade 1: mild; asymptomatic or mild symptoms. Grade 2: moderate. Grade 3: severe or medically significant but not immediately life threatening. Grade 4: life-threatening consequences. Grade 5: death. TEAEs were defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug.
    End point type
    Secondary
    End point timeframe
    up to 77 months
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    219 [31]
    225 [32]
    Units: percentage of participants
    191
    159
    Notes
    [31] - Safety Analysis Set
    [32] - Safety Analysis Set
    No statistical analyses for this end point

    Secondary: Change from Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population

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    End point title
    		 Change from Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Overall Population
    End point description
    The European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) contains 30 items and measures 5 functional dimensions (i.e., physical, role, emotional, cognitive, and social), 3 symptom items (i.e., fatigue, nausea/vomiting, and pain), 6 single items (i.e., dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health (GH) and quality of life (QoL) scale. For each scale and single item, a linear transformation was applied to standardize the scores between 0 (worst) and 100 (best) as described in the EORTC QLQ-C30 Scoring Manual.
    End point type
    Secondary
    End point timeframe
    Baseline (BL); End of Treatment (EOT) (up to 77 months)
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    226 [33]
    227 [34]
    Units: scores on a scale
    arithmetic mean (standard deviation)
        BL; Global Health Status/QoL Scale, n=223, 225
    59.19 ( 22.94 )
    59.89 ( 23.75 )
        Baseline; Physical Functioning, n=222, 225
    71.68 ( 23.05 )
    69.39 ( 24.60 )
        Baseline; Role Functioning, n=221, 226
    68.91 ( 30.84 )
    69.53 ( 31.48 )
        Baseline; Emotional Functioning, n=220, 224
    76.63 ( 22.24 )
    74.79 ( 25.05 )
        Baseline; Cognitive Functioning, n=222, 224
    82.81 ( 18.61 )
    81.41 ( 22.74 )
        Baseline; Social Functioning, n=222, 224
    74.74 ( 27.53 )
    73.93 ( 29.45 )
        Baseline, Fatigue, n=221, 223
    37.74 ( 26.69 )
    36.64 ( 27.28 )
        Baseline, Nausea and Vomiting, n=222, 225
    6.20 ( 15.26 )
    9.69 ( 21.25 )
        Baseline, Pain, n=220, 223
    28.25 ( 31.02 )
    27.36 ( 30.18 )
        Baseline, Dyspnoea, n=223, 227
    19.43 ( 25.13 )
    18.06 ( 25.70 )
        Baseline, Insomnia, n=223, 227
    30.64 ( 32.77 )
    29.22 ( 31.87 )
        Baseline, Loss of Appetite, n=222, 227
    20.27 ( 28.44 )
    22.17 ( 31.87 )
        Baseline, Constipation, n=223, 227
    15.25 ( 24.85 )
    14.83 ( 24.30 )
        Baseline, Diarrhoea, n=223, 225
    8.07 ( 17.46 )
    8.74 ( 21.07 )
        Baseline, Financial Impact, n=223, 225
    14.20 ( 24.97 )
    21.78 ( 28.26 )
        CFB at EOT; BL; GH Status/QoL Scale, n=128, 145
    -7.23 ( 22.56 )
    -7.99 ( 22.71 )
        CFB at EOT; BL; Phys Functioning, n=128, 144
    -13.59 ( 25.48 )
    -7.51 ( 22.95 )
        CFB at EOT; Role Functioning, n=128, 144
    -14.84 ( 33.87 )
    -10.88 ( 32.35 )
        CFB at EOT; Emotional Functioning, n=128, 144
    -5.60 ( 24.88 )
    -2.41 ( 24.83 )
        CFB at EOT; Cognitive Functioning, n=128, 145
    -7.29 ( 23.37 )
    -4.71 ( 24.67 )
        CFB at EOT; Social Functioning, n=128, 144
    -14.32 ( 31.56 )
    -4.98 ( 27.03 )
        CFB at EOT, Fatigue, n=128, 146
    11.89 ( 31.49 )
    10.24 ( 24.30 )
        CFB at EOT, Nausea and Vomiting, n=128, 145
    5.47 ( 18.37 )
    3.10 ( 25.00 )
        CFB at EOT, Pain, n=129, 145
    6.33 ( 30.42 )
    7.93 ( 33.11 )
        CFB at EOT, Dyspnoea, n=128, 145
    9.11 ( 34.93 )
    8.05 ( 28.40 )
        CFB at EOT, Insomnia, n=128, 146
    1.30 ( 36.80 )
    2.28 ( 33.37 )
        CFB at EOT, Loss of Appetite, n=128, 146
    16.15 ( 38.33 )
    9.36 ( 31.98 )
        CFB at EOT, Constipation, n=128, 146
    5.21 ( 33.58 )
    1.60 ( 28.05 )
        CFB at EOT, Diarrhoea, n=128, 145
    7.03 ( 28.26 )
    1.38 ( 28.02 )
        CFB at EOT, Financial Impact, n=128, 142
    2.08 ( 22.04 )
    1.17 ( 25.24 )
    Notes
    [33] - Full Analysis Set. Only participants with available data were analyzed.
    [34] - Full Analysis Set. Only participants with available data were analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup

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    End point title
    		 Change from Baseline (CFB) in the EORTC QLQ-C30 Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup
    End point description
    The European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) contains 30 items and measures 5 functional dimensions (i.e., physical, role, emotional, cognitive, and social), 3 symptom items (i.e., fatigue, nausea/vomiting, and pain), 6 single items (i.e., dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, (GH) and financial impact), and a global health and quality of life (QoL) scale. For each scale and single item, a linear transformation was applied to standardize the scores between 0 (worst) and 100 (best) as described in the EORTC QLQ-C30 Scoring Manual.
    End point type
    Secondary
    End point timeframe
    Baseline (BL); End of Treatment (EOT) (up to 77 months)
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    88 [35]
    74 [36]
    Units: scores on a scale
    arithmetic mean (standard deviation)
        BL; Global Health Status/QoL Scale, n=86, 74
    57.66 ( 22.37 )
    52.59 ( 24.13 )
        Baseline; Physical Functioning, n=86, 72
    68.60 ( 24.73 )
    64.30 ( 26.46 )
        Baseline; Role Functioning, n=85, 74
    65.89 ( 31.61 )
    60.59 ( 33.63 )
        Baseline; Emotional Functioning, n=85, 73
    76.10 ( 22.32 )
    67.61 ( 28.71 )
        Baseline; Cognitive Functioning, n=86, 74
    84.88 ( 18.72 )
    77.03 ( 23.84 )
        Baseline; Social Functioning, n=86, 73
    73.84 ( 27.00 )
    67.34 ( 31.87 )
        Baseline, Fatigue, n=85, 72
    39.02 ( 26.61 )
    43.62 ( 28.01 )
        Baseline, Nausea and Vomiting, n=86, 74
    6.20 ( 14.24 )
    15.77 ( 26.44 )
        Baseline, Pain, n=85, 72
    28.88 ( 32.38 )
    34.68 ( 32.50 )
        Baseline, Dyspnoea, n=86, 74
    21.32 ( 25.52 )
    21.62 ( 28.37 )
        Baseline, Insomnia, n=86, 74
    31.78 ( 30.64 )
    36.49 ( 33.64 )
        Baseline, Loss of Appetite, n=86, 74
    21.32 ( 27.49 )
    29.73 ( 36.00 )
        Baseline, Constipation, n=86, 74
    17.83 ( 26.91 )
    16.67 ( 27.72 )
        Baseline, Diarrhoea, n=86, 74
    7.75 ( 16.71 )
    9.01 ( 22.95 )
        Baseline, Financial Impact, n=86, 74
    13.57 ( 25.25 )
    24.32 ( 32.78 )
        CFB at EOT; BL; GH Status/QoL Scale, n=52, 42
    -6.57 ( 23.70 )
    -7.54 ( 30.84 )
        CFB at EOT; BL; Physical Functioning, n=51, 41
    -15.29 ( 25.83 )
    -11.83 ( 33.60 )
        CFB at EOT; Role Functioning, n=51, 41
    -19.61 ( 37.07 )
    -15.45 ( 41.06 )
        CFB at EOT; Emotional Functioning, n=52, 41
    -4.81 ( 28.02 )
    0.27 ( 33.98 )
        CFB at EOT; Cognitive Functioning, n=52, 42
    -7.69 ( 22.01 )
    -5.95 ( 30.54 )
        CFB at EOT; Social Functioning, n=52, 41
    -16.67 ( 27.42 )
    -2.44 ( 32.18 )
        CFB at EOT, Fatigue, n=51, 42
    13.51 ( 31.69 )
    13.10 ( 33.19 )
        CFB at EOT, Nausea and Vomiting, n=51, 41
    5.66 ( 14.78 )
    -3.66 ( 34.86 )
        CFB at EOT, Pain, n=52, 42
    8.65 ( 33.09 )
    7.94 ( 42.97 )
        CFB at EOT, Dyspnoea, n=51, 42
    9.15 ( 37.17 )
    7.94 ( 32.77 )
        CFB at EOT, Insomnia, n=51, 42
    5.88 ( 35.09 )
    -1.59 ( 41.62 )
        CFB at EOT, Loss of Appetite, n=51, 42
    20.26 ( 41.14 )
    10.32 ( 42.60 )
        CFB at EOT, Constipation, n=51, 42
    5.88 ( 32.46 )
    0.79 ( 30.79 )
        CFB at EOT, Diarrhoea, n=52, 42
    5.77 ( 21.61 )
    5.56 ( 30.28 )
        CFB at EOT, Financial Impact, n=52, 41
    2.56 ( 17.27 )
    7.32 ( 26.37 )
    Notes
    [35] - NK CC-Low FAS. Only participants with available data were analyzed.
    [36] - NK CC-Low FAS. Only participants with available data were analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population

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    End point title
    		 Change from Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Overall Population
    End point description
    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 [worst overall health] to 100 [best overall health]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health.
    End point type
    Secondary
    End point timeframe
    Baseline; End of Treatment (EOT) (up to 77 months)
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    226 [37]
    227 [38]
    Units: scores on a scale
    arithmetic mean (standard deviation)
        Baseline, Mobility Level, n=206, 212
    1.83 ( 0.969 )
    1.94 ( 1.054 )
        Baseline, Self-care Level, n=206, 212
    1.37 ( 0.771 )
    1.44 ( 0.861 )
        Baseline, Usual Activities, n=206, 212
    1.97 ( 1.086 )
    1.92 ( 1.063 )
        Baseline, Pain/Discomfort, n=206, 211
    2.04 ( 1.045 )
    2.08 ( 1.027 )
        Baseline, Anxiety/Depression, n=206, 212
    1.67 ( 0.844 )
    1.73 ( 0.907 )
        CFB at EOT, Mobility Level, n=118, 132
    0.47 ( 1.076 )
    0.25 ( 1.094 )
        CFB at EOT, Self-care Level, n=118, 132
    0.48 ( 1.052 )
    0.23 ( 0.946 )
        CFB at EOT, Usual Activities, n=118, 131
    0.42 ( 1.410 )
    0.31 ( 1.066 )
        CFB at EOT, Pain/Discomfort, n=118, 131
    0.29 ( 1.102 )
    0.09 ( 1.173 )
        CFB at EOT, Anxiety/Depression, n=118, 131
    0.33 ( 1.071 )
    0.21 ( 1.030 )
    Notes
    [37] - Full Analysis Set. Only participants with available data were analyzed.
    [38] - Full Analysis Set. Only participants with available data were analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup

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    End point title
    		 Change from Baseline (CFB) in EQ-5D-5L Dimension Scores at End of Treatment in the Natural Killer Cell Count-Low Subgroup
    End point description
    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 [worst overall health] to 100 [best overall health]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health.
    End point type
    Secondary
    End point timeframe
    Baseline; End of Treatment (EOT) (up to 77 months)
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    88 [39]
    74 [40]
    Units: scores on a scale
    arithmetic mean (standard deviation)
        Baseline, Mobility Level, n=78, 69
    2.09 ( 0.983 )
    2.04 ( 1.104 )
        Baseline, Self-care Level, n=78, 69
    1.49 ( 0.977 )
    1.54 ( 0.917 )
        Baseline, Usual Activities, n=78, 69
    2.03 ( 1.116 )
    2.14 ( 1.228 )
        Baseline, Pain/Discomfort, n=78, 68
    2.08 ( 1.054 )
    2.26 ( 1.060 )
        Baseline, Anxiety/Depression, n=78, 69
    1.65 ( 0.803 )
    1.96 ( 1.143 )
        CFB at EOT, Mobility Level, n=47, 39
    0.55 ( 1.080 )
    0.46 ( 1.315 )
        CFB at EOT, Self-care Level, n=47, 39
    0.53 ( 1.080 )
    0.41 ( 1.312 )
        CFB at EOT, Usual Activities, n=47, 38
    0.62 ( 1.392 )
    0.53 ( 1.224 )
        CFB at EOT, Pain/Discomfort, n=47, 38
    0.40 ( 1.173 )
    0.05 ( 1.469 )
        CFB at EOT, Anxiety/Depression, n=47, 38
    0.30 ( 1.250 )
    0.24 ( 1.324 )
    Notes
    [39] - NK CC-Low FAS. Only participants with available data were analyzed.
    [40] - NK CC-Low FAS. Only participants with available data were analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Overall Population

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    End point title
    		 Change from Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Overall Population
    End point description
    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 [worst overall health] to 100 [best overall health]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health.
    End point type
    Secondary
    End point timeframe
    Baseline; End of Treatment (EOT) (up to 77 months)
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    226 [41]
    227 [42]
    Units: scores on a scale
    arithmetic mean (standard deviation)
        Baseline, n=206, 211
    66.22 ( 20.5 )
    66.69 ( 20.4 )
        CFB at EOT, n=119, 129
    -8.10 ( 21.1 )
    -5.47 ( 23.2 )
    Notes
    [41] - Full Analysis Set. Only participants with available data were analyzed.
    [42] - Full Analysis Set. Only participants with available data were analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Natural Killer Cell Count-Low Subgroup

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    End point title
    		 Change from Baseline (CFB) in EQ-5D-5L VAS Score at End of Treatment in the Natural Killer Cell Count-Low Subgroup
    End point description
    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 [worst overall health] to 100 [best overall health]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health.
    End point type
    Secondary
    End point timeframe
    Baseline; End of Treatment (EOT) (up to 77 months)
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    88 [43]
    74 [44]
    Units: scores on a scale
    arithmetic mean (standard deviation)
        Baseline, n=78, 68
    65.87 ( 21.4 )
    58.65 ( 20.7 )
        CFB at EOT, n=48, 38
    -10.75 ( 21.0 )
    -7.53 ( 31.4 )
    Notes
    [43] - NK CC-Low FAS. Only participants with available data were analyzed.
    [44] - NK CC-Low FAS. Only participants with available data were analyzed.
    No statistical analyses for this end point

    Secondary: Tafasitamab serum concentrations

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    End point title
    		 Tafasitamab serum concentrations
    End point description
    Blood samples were collected for the assessment of serum concentrations of tafasitamab. The Pharmacokinetic (PK) Analysis Set was comprised of all participants who received at least one dose of tafasitamab and had at least one quantifiable serum tafasitamab concentration. 9999=Dispersion cannot be calculated for a single participant. Pharmacokinetic (PK) Analysis Set: all participants who received at least one dose of tafasitamab and had at least one quantifiable serum tafasitamab concentration.
    End point type
    Secondary
    End point timeframe
    pre-dose: Cycle 1 Days 1, 2, 3, 4, 15; Cycle 2 Days 1, 15; Cycle 3 Days 1, 15, Cycles 4, 5, 6, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35 Day 1. 1 hour post-dose: Cycle 1 Days 1, 4, 15; Cycle 2 Days 1, 15; Cycle 3 Days 1, 15
    End point values
    		 Tafasitamab + bendamustine Rituximab + bendamustine
    Number of subjects analysed
    219 [45]
    0 [46]
    Units: micrograms per milliliter (µg/mL)
    geometric mean (geometric coefficient of variation)
        Cycle 1 Day 1, pre-dose, n=218
    0.00 ( 58.8 )
    ( )
        Cycle 1 Day 1, 1 hour post-dose, n=40
    2.45 ( 37.1 )
    ( )
        Cycle 1 Day 2, pre-dose, n=215
    2.06 ( 30.2 )
    ( )
        Cycle 1 Day 3, pre-dose, n=211
    1.63 ( 30.4 )
    ( )
        Cycle 1 Day 4, pre-dose, n=209
    1.34 ( 33.5 )
    ( )
        Cycle 1 Day 4, 1 hour post-dose, n=169
    3.84 ( 31.8 )
    ( )
        Cycle 1 Day 15, pre-dose, n=198
    2.14 ( 39.1 )
    ( )
        Cycle 1 Day 15, 1 hour post-dose, n=168
    4.68 ( 31.9 )
    ( )
        Cycle 2 Day 1, pre-dose, n=197
    2.37 ( 55.1 )
    ( )
        Cycle 2 Day 1, 1 hour post-dose, n=160
    4.80 ( 32.8 )
    ( )
        Cycle 2 Day 15, pre-dose, n=174
    2.73 ( 42.4 )
    ( )
        Cycle 2 Day 15, 1 hour post-dose, n=152
    5.20 ( 44.4 )
    ( )
        Cycle 3 Day 1, pre-dose, n=174
    2.92 ( 43.5 )
    ( )
        Cycle 3 Day 1, 1 hour post-dose, n=134
    5.38 ( 32.2 )
    ( )
        Cycle 3 Day 15, pre-dose, n=159
    3.14 ( 38.3 )
    ( )
        Cycle 3 Day 15, 1 hour post-dose, n=136
    5.54 ( 30.1 )
    ( )
        Cycle 4 Day 1, pre-dose, n=150
    3.27 ( 5.54 )
    ( )
        Cycle 5 Day 1, pre-dose, n=133
    1.95 ( 54.6 )
    ( )
        Cycle 6 Day 1, pre-dose, n=118
    1.60 ( 61.2 )
    ( )
        Cycle 7 Day 1, pre-dose, n=91
    1.14 ( 75.3 )
    ( )
        Cycle 9 Day 1, pre-dose, n=66
    1.79 ( 50.3 )
    ( )
        Cycle 11 Day 1, pre-dose, n=50
    1.73 ( 58.1 )
    ( )
        Cycle 13 Day 1, pre-dose, n=46
    1.81 ( 66.4 )
    ( )
        Cycle 15 Day 1, pre-dose, n=39
    1.83 ( 55.8 )
    ( )
        Cycle 17 Day 1, pre-dose, n=33
    1.86 ( 48.3 )
    ( )
        Cycle 19 Day 1, pre-dose, n=30
    1.98 ( 36.4 )
    ( )
        Cycle 21 Day 1, pre-dose, n=32
    1.91 ( 52.0 )
    ( )
        Cycle 23 Day 1, pre-dose, n=31
    1.88 ( 55.2 )
    ( )
        Cycle 25 Day 1, pre-dose, n=7
    2.24 ( 37.7 )
    ( )
        Cycle 27 Day 1, pre-dose, n=2
    1.92 ( 12.6 )
    ( )
        Cycle 29 Day 1, pre-dose, n=2
    2.05 ( 21.3 )
    ( )
        Cycle 31 Day 1, pre-dose, n=2
    1.64 ( 23.9 )
    ( )
        Cycle 33 Day 1, pre-dose, n=1
    1.45 ( 9999 )
    ( )
        Cycle 35 Day 1, pre-dose, n=2
    1.51 ( 2.7 )
    ( )
    Notes
    [45] - PK Analysis Set. Only participants with available data were analyzed.
    [46] - PK was not assessed for rixuximab or for bendamustine.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    up to approximately 7.5 years
    Adverse event reporting additional description
    Adverse events have been reported for the Safety Analysis Set, comprised of all participants who received at least one dose of tafasitamab, bendamustine, or rituximab.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22
    Reporting groups
    Reporting group title
    Rituximab + bendamustine
    Reporting group description
    		 Participants received IV rituximab 375 mg/m^2 in combination with IV bendamustine 90 mg/m^2 in 28-day cycles for a maximum of 6 cycles. Participants received rituximab on Day 1 of each cycle until disease progression. Participants received bendamustine on either Days 2 and 3 or Days 1 and 2 of Cycles 1 to 6. Participants with an ongoing response of at least partial response at the end of Cycle 6, as per local assessment, continued tafasitamab or rituximab monotherapy per initially allocated treatment until disease progression. Treatment was stopped due to disease progression, unacceptable toxicity, death, or discontinuation for any other reason, whichever came first.

    Reporting group title
    Tafasitamab + bendamustine
    Reporting group description
    		 Participants received intravenous (IV) tafasitamab 12.0 milligrams per kilogram (mg/kg) in combination with IV bendamustine 90 mg/meters squared (m^2) in 28-day cycles for a maximum of 6 cycles. During Cycles 1 to 3, participants received tafastiamab on Days 1, 8, 15, and 22, plus a loading dose on Day 4 of Cycle 1. Participants received bendamustine on either Days 2 and 3 or Days 1 and 2 of Cycles 1 to 6. Participants with an ongoing response of at least partial response at the end of Cycle 6, as per local assessment, continued tafasitamab or rituximab monotherapy per initially allocated treatment until disease progression. Treatment was stopped due to disease progression, unacceptable toxicity, death, or discontinuation for any other reason, whichever came first.

    Serious adverse events
    		 Rituximab + bendamustine Tafasitamab + bendamustine
    Total subjects affected by serious adverse events
         subjects affected / exposed
    100 / 225 (44.44%)
    115 / 219 (52.51%)
         number of deaths (all causes)
    127
    129
         number of deaths resulting from adverse events
    33
    31
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    2 / 225 (0.89%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Bowen's disease
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    1 / 225 (0.44%)
    2 / 219 (0.91%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basosquamous carcinoma
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lung adenocarcinoma recurrent
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    2 / 225 (0.89%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasm
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    2 / 225 (0.89%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-small cell lung cancer recurrent
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Skin cancer
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 225 (0.44%)
    3 / 219 (1.37%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 225 (0.44%)
    3 / 219 (1.37%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour necrosis
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Aneurysm
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    2 / 225 (0.89%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 225 (0.44%)
    2 / 219 (0.91%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    3 / 225 (1.33%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    2 / 225 (0.89%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Discomfort
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 225 (0.44%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 225 (0.00%)
    3 / 219 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza like illness
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Illness
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Mucosal inflammation
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    5 / 225 (2.22%)
    9 / 219 (4.11%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Haemophagocytic lymphohistiocytosis
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Atelectasis
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial obstruction
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 225 (0.44%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Organising pneumonia
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 225 (0.00%)
    3 / 219 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumonitis
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device malfunction
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Compression fracture
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 225 (0.44%)
    2 / 219 (0.91%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Femoral neck fracture
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Flatback syndrome
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    3 / 225 (1.33%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Angina unstable
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 225 (0.44%)
    3 / 219 (1.37%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 225 (0.44%)
    2 / 219 (0.91%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Cardiac failure acute
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 225 (0.00%)
    2 / 219 (0.91%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiomyopathy
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    4 / 225 (1.78%)
    3 / 219 (1.37%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Myocardial infarction
         subjects affected / exposed
    1 / 225 (0.44%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Supraventricular tachyarrhythmia
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Ventricular tachycardia
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Limbic encephalitis
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral sensorimotor neuropathy
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post herpetic neuralgia
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Syncope
         subjects affected / exposed
    3 / 225 (1.33%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxic encephalopathy
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    6 / 225 (2.67%)
    4 / 219 (1.83%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphopenia
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelosuppression
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    4 / 225 (1.78%)
    5 / 219 (2.28%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 225 (0.44%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Macular oedema
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 225 (0.44%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 225 (0.00%)
    2 / 219 (0.91%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum oesophageal
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysbiosis
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    2 / 225 (0.89%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mouth ulceration
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal haemorrhage
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal perforation
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Vomiting
         subjects affected / exposed
    3 / 225 (1.33%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cirrhosis
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Drug eruption
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug reaction with eosinophilia and systemic symptoms
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pruritus
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 225 (0.89%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Azotaemia
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 225 (0.44%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal infection
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bacteraemia
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    2 / 225 (0.89%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    6 / 225 (2.67%)
    9 / 219 (4.11%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 9
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    COVID-19 pneumonia
         subjects affected / exposed
    6 / 225 (2.67%)
    4 / 219 (1.83%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 6
    0 / 4
    Cellulitis
         subjects affected / exposed
    2 / 225 (0.89%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Central nervous system infection
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridial sepsis
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcal sepsis
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Device related infection
         subjects affected / exposed
    1 / 225 (0.44%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disseminated tuberculosis
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Febrile infection
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemophilus sepsis
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes simplex
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 225 (0.00%)
    4 / 219 (1.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster disseminated
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster reactivation
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 225 (0.44%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    3 / 225 (1.33%)
    3 / 219 (1.37%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    5 / 225 (2.22%)
    3 / 219 (1.37%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella infection
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Large intestine infection
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    0 / 225 (0.00%)
    3 / 219 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Oropharyngeal candidiasis
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    17 / 225 (7.56%)
    26 / 219 (11.87%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 29
         deaths causally related to treatment / all
    0 / 1
    0 / 8
    Pneumonia bacterial
         subjects affected / exposed
    2 / 225 (0.89%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pharyngitis
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parainfluenzae virus infection
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 225 (0.44%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    2 / 225 (0.89%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia streptococcal
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumonia staphylococcal
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    4 / 225 (1.78%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Sepsis
         subjects affected / exposed
    5 / 225 (2.22%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Salmonella bacteraemia
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicella zoster virus infection
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 225 (0.44%)
    2 / 219 (0.91%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    2 / 225 (0.89%)
    3 / 219 (1.37%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal sepsis
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weil's disease
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 225 (0.44%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 225 (0.44%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 225 (0.44%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 225 (0.00%)
    1 / 219 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour lysis syndrome
         subjects affected / exposed
    2 / 225 (0.89%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vitamin B12 deficiency
         subjects affected / exposed
    1 / 225 (0.44%)
    0 / 219 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Rituximab + bendamustine Tafasitamab + bendamustine
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    199 / 225 (88.44%)
    206 / 219 (94.06%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    11 / 225 (4.89%)
    13 / 219 (5.94%)
         occurrences all number
    13
    16
    Hypotension
         subjects affected / exposed
    12 / 225 (5.33%)
    17 / 219 (7.76%)
         occurrences all number
    12
    18
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    25 / 225 (11.11%)
    40 / 219 (18.26%)
         occurrences all number
    32
    51
    Fatigue
         subjects affected / exposed
    37 / 225 (16.44%)
    56 / 219 (25.57%)
         occurrences all number
    45
    78
    Pyrexia
         subjects affected / exposed
    35 / 225 (15.56%)
    38 / 219 (17.35%)
         occurrences all number
    49
    57
    Oedema peripheral
         subjects affected / exposed
    17 / 225 (7.56%)
    25 / 219 (11.42%)
         occurrences all number
    18
    30
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    25 / 225 (11.11%)
    41 / 219 (18.72%)
         occurrences all number
    33
    68
    Dyspnoea
         subjects affected / exposed
    18 / 225 (8.00%)
    28 / 219 (12.79%)
         occurrences all number
    21
    33
    Productive cough
         subjects affected / exposed
    6 / 225 (2.67%)
    13 / 219 (5.94%)
         occurrences all number
    6
    19
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    18 / 225 (8.00%)
    20 / 219 (9.13%)
         occurrences all number
    21
    22
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    10 / 225 (4.44%)
    11 / 219 (5.02%)
         occurrences all number
    16
    14
    Aspartate aminotransferase increased
         subjects affected / exposed
    8 / 225 (3.56%)
    12 / 219 (5.48%)
         occurrences all number
    13
    15
    Blood creatinine increased
         subjects affected / exposed
    10 / 225 (4.44%)
    18 / 219 (8.22%)
         occurrences all number
    17
    25
    Weight decreased
         subjects affected / exposed
    20 / 225 (8.89%)
    15 / 219 (6.85%)
         occurrences all number
    20
    15
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    15 / 225 (6.67%)
    8 / 219 (3.65%)
         occurrences all number
    15
    8
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    7 / 225 (3.11%)
    13 / 219 (5.94%)
         occurrences all number
    7
    14
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    14 / 225 (6.22%)
    26 / 219 (11.87%)
         occurrences all number
    15
    32
    Headache
         subjects affected / exposed
    25 / 225 (11.11%)
    30 / 219 (13.70%)
         occurrences all number
    36
    38
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    48 / 225 (21.33%)
    60 / 219 (27.40%)
         occurrences all number
    73
    94
    Leukopenia
         subjects affected / exposed
    14 / 225 (6.22%)
    21 / 219 (9.59%)
         occurrences all number
    40
    37
    Lymphopenia
         subjects affected / exposed
    19 / 225 (8.44%)
    20 / 219 (9.13%)
         occurrences all number
    39
    26
    Neutropenia
         subjects affected / exposed
    98 / 225 (43.56%)
    116 / 219 (52.97%)
         occurrences all number
    347
    304
    Thrombocytopenia
         subjects affected / exposed
    60 / 225 (26.67%)
    67 / 219 (30.59%)
         occurrences all number
    101
    112
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    41 / 225 (18.22%)
    50 / 219 (22.83%)
         occurrences all number
    46
    63
    Diarrhoea
         subjects affected / exposed
    43 / 225 (19.11%)
    58 / 219 (26.48%)
         occurrences all number
    61
    103
    Dyspepsia
         subjects affected / exposed
    14 / 225 (6.22%)
    18 / 219 (8.22%)
         occurrences all number
    15
    24
    Abdominal pain
         subjects affected / exposed
    15 / 225 (6.67%)
    31 / 219 (14.16%)
         occurrences all number
    16
    41
    Nausea
         subjects affected / exposed
    62 / 225 (27.56%)
    77 / 219 (35.16%)
         occurrences all number
    92
    133
    Vomiting
         subjects affected / exposed
    22 / 225 (9.78%)
    31 / 219 (14.16%)
         occurrences all number
    38
    43
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    26 / 225 (11.56%)
    10 / 219 (4.57%)
         occurrences all number
    32
    18
    Rash
         subjects affected / exposed
    14 / 225 (6.22%)
    18 / 219 (8.22%)
         occurrences all number
    18
    22
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    11 / 225 (4.89%)
    15 / 219 (6.85%)
         occurrences all number
    11
    19
    Back pain
         subjects affected / exposed
    26 / 225 (11.56%)
    16 / 219 (7.31%)
         occurrences all number
    30
    19
    Pain in extremity
         subjects affected / exposed
    9 / 225 (4.00%)
    15 / 219 (6.85%)
         occurrences all number
    10
    20
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    12 / 225 (5.33%)
    9 / 219 (4.11%)
         occurrences all number
    13
    10
    Nasopharyngitis
         subjects affected / exposed
    14 / 225 (6.22%)
    13 / 219 (5.94%)
         occurrences all number
    17
    15
    Upper respiratory tract infection
         subjects affected / exposed
    21 / 225 (9.33%)
    18 / 219 (8.22%)
         occurrences all number
    31
    29
    Urinary tract infection
         subjects affected / exposed
    20 / 225 (8.89%)
    17 / 219 (7.76%)
         occurrences all number
    31
    21
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    15 / 225 (6.67%)
    16 / 219 (7.31%)
         occurrences all number
    33
    31
    Decreased appetite
         subjects affected / exposed
    36 / 225 (16.00%)
    47 / 219 (21.46%)
         occurrences all number
    45
    63
    Hypokalaemia
         subjects affected / exposed
    30 / 225 (13.33%)
    28 / 219 (12.79%)
         occurrences all number
    41
    48
    Hypomagnesaemia
         subjects affected / exposed
    7 / 225 (3.11%)
    13 / 219 (5.94%)
         occurrences all number
    10
    15

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    25 Nov 2015
    A summary of changes is not available.
    18 Dec 2015
    A summary of changes is not available.
    04 Mar 2016
    A summary of changes is not available.
    21 Nov 2016
    The primary purpose of the amendment was to clarify and add secondary objectives and endpoints and to update eligibility criteria.
    05 Apr 2017
    The primary purpose of this protocol amendment was to update eligibility criteria.
    21 Jul 2017
    The primary purpose of this amendment was to outline the continuation of antibody monotherapy treatment in accordance with the original treatment allocation until disease progression and to clarify exclusion criteria.
    23 Aug 2017
    The primary purpose of this amendment was to outline the continuation of antibody monotherapy treatment in accordance with the original treatment allocation until disease progression and to clarify exclusion criteria.
    14 Feb 2019
    The primary purpose of this amendment was to introduce the co-primary endpoint to evaluate progression-free survival (PFS) in the natural killer cell count (NKCC)-low population in addition to evaluate PFS in the overall population.
    22 Dec 2021
    The primary purpose of this amendment was to remove duration of response from the key secondary endpoints for hierarchical statistical testing and to clarify that event-driven primary analysis would not be performed because time-driven final analysis was projected to be reached before the event-driven primary analysis.
    02 Dec 2022
    The primary purpose of the amendment was to include details on the final analysis for overall survival.
    10 Apr 2024
    The primary purpose of the amendment was to update the sponsorship from MorphoSys AG to Incyte Corporation.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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