Amendment 1 Research Protocol Patient population: patients aged 18 years or older with recurrent WM, with ≥1 line of prior systemic treatment instead of 1–3 lines of prior systemic treatment. Clarification of inclusion and exclusion criteria. Adjustment of contraception requirements for women using rituximab. Adjustment and clarification of timing for clinical evaluations. Subject Information Sheet and Consent Form 5. Adjustment of contraception requirements for women using rituximab. 6. Adjustment and clarification of timing for clinical evaluations. Participating Hospitals 7. Addition of LUMC, Tergooi hospitals, and IJsselland hospital. 8. Change of local investigator at Erasmus MC.

Amendment 2 The labeling of the study medication ixazomib citrate will be taken over by the central pharmacy at the Academic Medical Center, Amsterdam.

Amendment 3 Other changes: In the updated ixazomib citrate Investigator’s Brochure (IB, version 10), a fatal case of progressive multifocal leukoencephalopathy (PML) was reported in a patient treated with ixazomib citrate. It is not known whether ixazomib citrate contributed to the development of this condition in the patient. This information has been added to the patient information. Additional changes: Administrative correction of text regarding urine tests that was incorrect in the patient information. For already included patients, a summary of the patient information has been prepared. A new version of the Investigator’s Brochure for ixazomib dated June 27, 2016 (version 10) and NLN9708 risk language April 20, 2016, along with the statement from the principal investigator, Prof. Dr. M. J. Kersten, indicating that the new IB has implications for the HOVON 124 study. Annual progress and safety reporting.

Amendment 4 Reason for this change: Clarification of trial-specific procedures: Warm measurement of serum IgM in case of cryoglobulinemia. This is crucial for correct response assessment. The method of response assessment based on CT images. Although reference was made to the article by Cheson et al., these criteria were not clearly incorporated into the protocol. The time points when response evaluation should be performed. SAE (Serious Adverse Events) can now be reported by email. The inclusion period has been extended by 2 years due to delayed enrollment of patients. The KWF (Dutch Cancer Society) has agreed to a cost-neutral extension.

Amendment 5 Reason for this change: Protocol: Textual, non-substantial adjustments. Patient Information: Update regarding privacy legislation, non-substantial. Change of local investigator: Dr. Koene replaces Dr. Vos at St. Antonius Hospital in Nieuwegein.

Amendment 6 Reason for this change: Dr. Silbermann replaces Dr. Deenik at Tergooi Hospital in Hilversum.