The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study (NCT02181413) demonstrated improved progression-free survival with ixazomib maintenance versus placebo post autologous stem cell transplant (ASCT) in multiple myeloma patients. We report additional safety data from TOURMALINE-MM3 to inform adverse event (AE) management recommendations. Patients were randomized 3:2 to receive ixazomib (n = 395) or placebo (n = 261) on days 1, 8, and 15 of 28-day cycles for ~ 2 years or until progressive disease/toxicity. The initial 3-mg ixazomib dose was escalated to 4 mg in cycle 5, if tolerated in cycles 1-4. Safety was a secondary endpoint assessed in all treated patients; AEs were graded using Common Terminology Criteria for AEs v4.03. The rate of grade ≥ 3 AEs was higher in the ixazomib arm (19%) than in the placebo arm (5%), but the rate of discontinuation due to AEs was similar (7% vs. 5%). For AEs of clinical interest, rates were higher with ixazomib versus placebo: nausea 39% versus 15%, vomiting 27% versus 11%, diarrhea 35% versus 24%, thrombocytopenia 13% versus 3%, and peripheral neuropathy 19% versus 15%. However, the majority of events were low-grade, manageable with supportive therapy or dose reduction, and reversible, and did not result in discontinuation. There was no evidence of cumulative, long-term, or late-onset toxicity with ixazomib maintenance. Ixazomib is an efficacious and tolerable option for post-ASCT maintenance. AEs associated with ixazomib maintenance can be managed in the context of routine post-ASCT supportive care due to the limited additional toxicity. ClinicalTrials.gov NCT02181413.

Department of Haematology The Royal Marsden Hospital London UK

Department of Hematology Ankara University Ankara Turkey

Department of Hematology University Hospital Hôtel Dieu Nantes France

Department of Hematology University Hospital of Salamanca CIC IBM CC Salamanca Spain

Department of Hematooncology University Hospital Ostrava Ostrava Czech Republic

Division of Hematology Department of Internal Medicine Mayo Clinic Rochester MN USA

Division of Molecular Pathology The Institute of Cancer Research and The Royal Marsden Hospital 123 Old Brompton Road London SW7 3RP UK

Hematology and Medical Oncology Department of Clinical Therapeutics School of Medicine National and Kapodistrian University of Athens Athens Greece

Malignant Haematology and Stem Cell Transplantation Service Alfred Health Monash University Melbourne Australia

Millennium Pharmaceuticals Inc a wholly owned subsidiary of Takeda Pharmaceutical Company Limited Cambridge MA USA

Oslo Myeloma Center Oslo University Hospital and KG Jebsen Center for B Cell Malignancies University of Oslo Oslo Norway

Servicio de Hematología y Oncología Médica Hospital Universitario Morales Meseguer y Centro Regional de Hemodonación IMIB Arrixaca Universidad de Murcia Murcia Spain

Ann Hematol. 2021 Jan;100(1):297-302. doi: 10.1007/s00277-020-04302-0. PubMed

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Management of patients with multiple myeloma beyond the clinical-trial setting: understanding the balance between efficacy, safety and tolerability, and quality of life

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ClinicalTrials.gov
NCT02181413