Abstract
Triplet combinations containing a proteasome inhibitor are a standard of care in newly diagnosed multiple myeloma (NDMM). We examined the long-term efficacy and safety of the all-oral combination of weekly ixazomib plus lenalidomide-dexamethasone (IRd), followed by single-agent ixazomib maintenance in NDMM patients. Of 65 enrolled patients, 53 received ixazomib 4 mg (days 1, 8, and 15) plus lenalidomide 25 mg (days 1-21) and dexamethasone 40 mg (days 1, 8, 15, and 22) for up to twelve 28-day induction cycles. Twenty-three patients discontinued induction for stem cell transplantation (SCT). In the remaining 42 patients, overall response rate was 80%, including 63% ≥very good partial response (VGPR) and 32% complete responses. At a median follow-up of 56 months, median progression-free survival (PFS) was 35.4 months in the total population. Twenty-five patients received ixazomib maintenance; eight deepened their response (76% ≥VGPR), and median PFS was 37.2 months in this subgroup. Nine of 42 patients who did not proceed to SCT (14% of total population) had an adverse event requiring discontinuation. Ixazomib (median ≥ 96%) and lenalidomide (median 88-94%) relative dose intensities were maintained throughout treatment. Weekly IRd, followed by ixazomib maintenance, was highly active with acceptable toxicity, enabling long-term administration with no evidence of cumulative toxicities.