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

Martin Kaiser, Meral Beksaç, Nina Gulbrandsen, Fredrik Schjesvold, Roman Hájek, Philippe Moreau, Felipe de Arriba de la Fuente, María Victoria Mateos, Sharon West, Andrew Spencer, S. Vincent Rajkumar, Kaveri Suryanarayan, Michael Czorniak, Cong Li, Zhaoyang Teng, Richard Labotka, Meletios A. Dimopoulos

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)1793-1804
Number of pages12
JournalAnnals of hematology
Volume99
Issue number8
DOIs
StatePublished - Aug 1 2020

Keywords

  • Adverse events
  • Ixazomib
  • Maintenance therapy
  • Multiple myeloma
  • Safety

ASJC Scopus subject areas

  • Hematology

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    Kaiser, M., Beksaç, M., Gulbrandsen, N., Schjesvold, F., Hájek, R., Moreau, P., de Arriba de la Fuente, F., Mateos, M. V., West, S., Spencer, A., Rajkumar, S. V., Suryanarayan, K., Czorniak, M., Li, C., Teng, Z., Labotka, R., & Dimopoulos, M. A. (2020). Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma. Annals of hematology, 99(8), 1793-1804. https://doi.org/10.1007/s00277-020-04149-5