Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma

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ORIGINAL ARTICLE

Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma Martin Kaiser 1,2 & Meral Beksaç 3 & Nina Gulbrandsen 4 & Fredrik Schjesvold 4 & Roman Hájek 5 & Philippe Moreau 6 & Felipe de Arriba de la Fuente 7 & María-Victoria Mateos 8 & Sharon West 1 & Andrew Spencer 9 & S. Vincent Rajkumar 10 & Kaveri Suryanarayan 11 & Michael Czorniak 11 & Cong Li 11 & Zhaoyang Teng 11 & Richard Labotka 11 & Meletios A. Dimopoulos 12 Received: 12 May 2020 / Accepted: 14 June 2020 # The Author(s) 2020

Abstract 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 28day 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 Keywords Adverse events . Ixazomib . Maintenance therapy . Multiple myeloma . Safety

* Martin Kaiser [email protected]

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

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Department of Haematology, The Royal Marsden Hospital, London, UK

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

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

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

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

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Millennium Pharmaceuti