TOURMALINE-MM4 trial of ixazomib maintenance meets primary endpoint

TOURMALINE-MM4 is a phase III study designed to compare single-agent ixazomib maintenance to placebo in patients with newly diagnosed multiple myeloma (NDMM) who were not treated with a stem cell transplant (SCT). On the 7^th November 2019 it was announced that the TOURMALINE-MM4 trial had met its primary endpoint of prolonging progression-free survival (PFS) compared to placebo.¹ 

TOURMALINE-MM4 (NCT02312258)^1,2

• Phase III, randomized, placebo-controlled, double-blind study in adult patients with NDMM who were not treated with SCT (N= 706)¹
  • Patients had received 6­–12 months of initial therapy¹
  • Patients must have achieved a partial response or better to this initial therapy¹
• Trial arms: single-agent ixazomib versus placebo¹
  • Ixazomib (3mg, or placebo capsule) was orally administered on Day 1, 8, and 15 of each 28-day cycle for up to 26 cycles²
  • Dose reductions were permitted if a patient experienced an adverse event associated with the study drug (3mg, 2.3mg, 1.5mg, and discontinuation)²
• Primary endpoint: PFS
  • Defined as time from date of randomization to date of first documented disease progression or death from any cause, as per independent review committee evaluation²
• Secondary endpoints include: overall survival, time to progression, and percentage of patients converting from minimal residual disease (MRD)-positive to MRD-negative responses²
• This is the first phase III study to use a maintenance therapy that was not part of the initial induction therapy¹

Results¹

• Efficacy:
  • The study met its primary endpoint of prolonging PFS compared to placebo
• Safety:
  • The safety profile of ixazomib in the maintenance setting was consistent with that reported of single-agent use, with no new safety signals
• The pharmaceutical company responsible for the trial are expecting to submit the full data results for presentation at an upcoming meeting¹

Context¹

There are several ongoing TOURMALINE trials investigating ixazomib as monotherapy or ixazomib in combination with other agents in different multiple myeloma (MM) patient populations.¹ The TOURMALINE-MM1 study is comparing ixazomib + lenalidomide + dexamethasone (Ixa-Rd) to placebo + Rd in patients with relapsed/refractory MM, whilst the TOURMALINE-MM3 trial is comparing ixazomib to placebo as maintenance in patients with NDMM following induction and autologous SCT. The results of the TOURMALINE-MM3 study were presented at the American Society of Hematology (ASH) meeting, 2018, and are available here.³