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

Ann Hematol. 2020 Aug;99(8):1793-1804. doi: 10.1007/s00277-020-04149-5. Epub 2020 Jul 1.


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. NCT02181413.

Keywords: Adverse events; Ixazomib; Maintenance therapy; Multiple myeloma; Safety.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Autografts
  • Boron Compounds / administration & dosage
  • Boron Compounds / adverse effects
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Glycine / administration & dosage
  • Glycine / adverse effects
  • Glycine / analogs & derivatives
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma* / mortality
  • Multiple Myeloma* / therapy
  • Silicates / administration & dosage
  • Silicates / adverse effects
  • Stem Cell Transplantation*
  • Survival Rate


  • Boron Compounds
  • Silicates
  • tourmaline
  • ixazomib
  • Glycine

Associated data