Evidence from the TOURMALINE-MM1 trialr
© NEJM 2016
PFS benefit was seen across all subgroups, including high-risk cytogenetics. Responses were rapid in both arms (1.1 vs. 1.9 months) and appeared to be durable, particularly in the ixazomib arm. Responses deepened with duration of exposure in the ixazomib arm.
Cumulative best responses over time in the intent-to-treat population
A= ixazomib group, B= placebo group.
© NEJM 2016
Evidence from the Kumar et al, 2019 studyr
Further evidence for the activity of the ixazomib, lenalidomide and dexamethasone activity in multiple myeloma was presented by Kumar et alr. While this study was in the newly diagnosed multiple myeloma (NDMM) population, and included maintenance therapy as a subset, it is further evidence of the activity of this triplet combination.
The primary objectives were to determine the combined rate of CR and VGPR, and the tolerability and toxicity of the ixazomib, lenalidomide and dexamethasone triplet in patients with NDMM. The secondary objectives included determination of ORR, measures of response durability and OS. 65 patients were enrolled (15 in the phase 1 component and 50 in phase 2) in this open-label, dose-escalation, phase 1/2 study. Of enrolled patients, 53 received triplet therapy at the target dose (Ixazomib 4 mg Day 1, 8 and 15; Lenalidomide 25 mg Day 1-21 and Dexamethasone 40 mg Days 1, 8, 15 and 22 of a 28-day cycle) for up to 12 induction cycles. 23 patients moved to AutoSCT after a median of 6 cycles of induction treatment at the discretion of the primary physician, and were excluded from the subsequent analysis.
In the remaining 42 patients, at median follow-up of 56 months, ORR was 80%, with 32% CR rate (10% stringent CR). Dose delivery, and by deduction tolerability was >96% for ixazomib, and 88.3 – 93.7% for lenalidomide. As was found in the TOURMALINE-MM1 trial, depth of response to this triplet improved with duration of exposure, as evidenced by the proportion pf patients achieving VGPR or better increasing over time (pictured, left). A similar pattern was seen in patients regardless of transplant status.
© Leukaemia 2019
Median PFS overall was 35.4 months (pictured, right), with median PFS 29.4 months in those not transplanted, compared to 37.2 in those who underwent AutoSCT.r