Treatment Regimens for Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma: A Systematic Literature Review and Network Meta-analysis.

INTRODUCTION: Many treatment regimens have been evaluated in transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). The objective of this study was to compare the efficacy of relevant therapies for the treatment of TIE patients with NDMM. METHODS: Progression-free survival (PFS) and overall survival (OS) from large randomised controlled trials (RCTs) evaluating different treatment options for TIE patients with NDMM were compared in a network meta-analysis (NMA). The NMA includes recent primary and long-term OS readouts from SWOG S0777, ENDURANCE, MAIA, and ALCYONE. Relevant trials were identified through a systematic literature review. Relative efficacy measures (i.e., hazard ratios [HRs] for PFS and OS) were extracted and synthesised in random-effects NMAs. RESULTS: A total of 122 publications describing 45 unique RCTs was identified. Continuous lenalidomide/dexamethasone (Rd) was selected as the referent comparator. Daratumumab-containing treatments (daratumumab/lenalidomide/dexamethasone [D-Rd], daratumumab/bortezomib/melphalan/prednisone [D-VMP]) and bortezomib/lenalidomide/dexamethasone (VRd) had the highest probabilities of being more effective than Rd continuous for PFS (HR: D-Rd, 0.53; D-VMP, 0.57, VRd, 0.77) and OS (HR: D-Rd, 0.68; VRd, 0.77, D-VMP, 0.78). D-Rd had the highest chance of being ranked as the most effective treatment with respect to PFS and OS. Results using a smaller network focusing on only those regimens that are relevant in Europe were consistent with the primary analysis. CONCLUSIONS: These comparative effectiveness data may help inform treatment selection in TIE patients with NDMM.

A matching-adjusted indirect treatment comparison (MAIC) of daratumumab-bortezomib-melphalan-prednisone (D-VMP) versus lenalidomide-dexamethasone continuous (Rd continuous), lenalidomide-dexamethasone 18 months (Rd 18), and melphalan-prednisone-thalidomide (MPT).

D-VMP is a novel treatment for transplant-ineligible newly diagnosed multiple myeloma (TIE NDMM). D-VMP significantly prolonged PFS versus VMP in the ALCYONE trial. The FIRST trial investigated Rd given in 28-day cycles until disease progression, Rd for 18 cycles, and MPT for 12 cycles for TIE NDMM. As no randomized controlled trials comparing D-VMP to standard-of-care regimens such as those in FIRST are available, an MAIC was performed to assess relative OS and PFS for D-VMP from ALYCONE and Rd continuous, Rd 18, and MPT from FIRST. Individual patient data for D-VMP in ALCYONE were weighted to match aggregated baseline patient characteristics for each arm of FIRST. D-VMP significantly improved OS versus MPT and Rd 18, with a trend favoring D-VMP versus Rd continuous. D-VMP performed significantly better than all FIRST comparators for PFS. This MAIC demonstrates OS and PFS benefits for D-VMP versus Rd continuous, Rd 18, and MPT.