On March 10, 2020, Takeda Pharmaceutical provided the following press release regarding their upfront phase 3 trial in newly diagnosed multiple myeloma patients of ixazomib/lenalidomide/dexamethasone versus lenalidomide/dexamethasone:
Takeda Pharmaceutical Company Limited today announced the results from the TOURMALINE-MM2 study designed to evaluate the addition of NINLARO™ (ixazomib) to lenalidomide and dexamethasone in newly diagnosed transplant ineligible multiple myeloma patients. The addition of ixazomib to lenalidomide and dexamethasone resulted in an improvement in median progression-free survival (PFS) of 13.5 months (35.3 months versus 21.8 months; hazard ratio [HR] 0.83; p=0.073); however, it did not meet the threshold for statistical significance. The safety profile associated with NINLARO from the TOURMALINE-MM2 trial was generally consistent with the existing prescribing information.
This was absolutely unexpected findings as in the relapse setting, patients with 1-3 prior therapies, the same phase 3 format of IRd vs Rd showed a statistically superior PFS for the triplet combination (~ 6 months improvement). The myeloma community was anxiously awaiting the results of the upfront trial, the option of an all oral regimen is quite attractive in many situations. Further, with the exception of the recent phase 3 elotuzumab/lenalidomide/dexamethasone trial (Eloquent-1), almost all trials comparing a triplet to a doublet regimen in either upfront or relapsed myeloma, demonstrated an advantage for the triplet regimen. We now have TWO upfront phase 3 trials which do not show the advantage of a triplet over a doublet. That stated, although the primary endpoint was not observed, the study did show an improvement in PFS of ~ 35 months vs ~ 22 months (although HR 0.73, p = 0.73), indicating a "trend" toward superiority. Thus, for those patients who cannot travel for intravenous therapy, the combination of ixazomib/lenalidomide/dexamethasone may still be a consideration.