Ixazomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma: long-term follow-up including ixazomib maintenance

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.

Conflict of interest statement

SKK: consulting fees, paid to institution, from Celgene, Takeda, Janssen, KITE, Merck, Abbvie, Medimmune, Genentech, Oncopeptides, and Amgen. JGB: institutional research funding from Abbvie, Amgen, Bluebird, BMS, Celgene, Genentech, Glenmark, Janssen, Novartis, Poseida, Takeda, and Teva. RN: membership of advisory council or committee, consulting fees, and grants or funds from Takeda, Celgene, BMS, Amgen, and Janssen. SL: personal fees as a consultant for Millennium Pharmaceuticals Inc., Celgene, Novartis, BMS, Onyx, and Janssen, outside the submitted work. MH: membership of advisory council or committee for Pharmacyclics and Medimmune, honoraria from Celgene and Sanofi, consulting fees from Cellerant, and grants or funds from Takeda and Otsuka. AKS: consultant for: Amgen, Celgene, BMS, Janssen, Ono, and Takeda. PH: membership of advisory council or committee, and honoraria from Millennium/Takeda and Celgene. RV: honoraria from Takeda. JLK: grant from Millennium Pharmaceuticals, Inc. during the conduct of the study. Grants from Celgene, Merck, and Novartis, and personal fees from Millennium Pharmaceuticals, Inc., Celgene, Onyx, Spectrum, Novartis, and Janssen, outside the conduct of the study. DB and EL: employment, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. PGR: consulting fees from Takeda and Celgene. The remaining authors declare that they have no conflict of interest.

Figures

Fig. 1

Changes in response rates during induction and maintenance. a Deepening of response during the maintenance phase, b kinetics of response during induction and maintenance in all patients (N = 64), c kinetics of response during induction and maintenance in patients who did not proceed to stem cell transplantation (N = 41), and d kinetics of response during induction and maintenance in patients who received maintenance (N = 25)

Fig. 2

Progression-free survival in a all patients*, b those who did not proceed to SCT and c those who received maintenance therapy. *Patients who received SCT were censored at the time of SCT