OA-44: Pomalidomide, bortezomib, and dexamethasone vs bortezomib and dexamethasone in relapsed or refractory multiple myeloma (OPTIMISMM): final survival outcomes from a randomized, open-label, phase 3 trial

Introduction: Pomalidomide (POM) is an oral immunomodulatory drug with direct tumoricidal and immunomodulatory efficacy in lenalidomide (LEN)-refractory relapsed or refractory multiple myeloma (RRMM). POM, bortezomib (BORT), and dexamethasone (DEX; PVd) is a preferred option in patients (pts) who have received ≥1 prior therapies, including those who have received LEN and BORT. In the primary analysis of OPTIMISMM, pts had significantly prolonged median progression-free survival (PFS) with PVd versus BORT + DEX (Vd; 11.2 vs 7.1 months; HR 0.61; P< 0.0001), with a safety profile consistent with known adverse events (AEs) of the individual components. Here, we report results from the final overall survival (OS) analysis of pts treated with PVd versus Vd in OPTIMISMM.

Methods: Eligible pts had a diagnosis of RRMM, received 1–3 prior lines of therapy (including ≥1 LEN-containing regimen), an ECOG performance status of ≤2, and documented disease progression during or after their last anti-myeloma therapy. OS was a secondary endpoint and was defined as time from randomization to death from any cause. OS was compared between arms using a log-rank test (with an overall 2-sided significance level of 5%) stratified by the 3 baseline factors used for randomization. Kaplan–Meier method was used to estimate the survival distribution functions for each arm. Median OS and 2-sided 95% CI for the median were estimated. A Cox proportional hazards model stratified by the 3 baseline factors was used to estimate HR and 95% CIs.

Results: In the intent-to-treat population (N=559), 281 and 278 pts had ongoing PVd and Vd treatment, respectively; median duration of treatment was 41.2 and 21.4 months. In this final analysis of OS, the OS data were mature (overall event rate, 70.0%). With median follow-up of 64.5 months for surviving pts (data cutoff May 13, 2022), median OS was numerically longer with PVd versus Vd (35.6 vs 31.6 months; HR [95% CI], 0.94 [0.77–1.15]; P=0.571). Median PFS2 was longer in pts treated with PVd versus Vd (22.1 vs 16.9 months; HR [95% CI], 0.77 [0.64–0.94]; nominal P=0.008). Updated PFS and safety data were consistent with the primary analysis. Time to treatment failure was longer with PVd versus Vd (8.8 vs 4.6 months). The most common treatment-emergent AEs (TEAEs) with PVd were neutropenia (54%), peripheral sensory neuropathy (48%), and thrombocytopenia (40%); with Vd these were thrombocytopenia (39%), peripheral sensory neuropathy (38%), and diarrhea (31%). The most common TEAE leading to treatment discontinuation was peripheral neuropathy (PVd, 11%; Vd, 8%); death occurred in 196 (71%) pts treated with PVd and 190 (70%) pts treated with Vd.

Conclusions: These findings from OPTIMISMM showed a slight, nonsignificant trend towards improved OS with PVd versus Vd. PFS2 was also improved with PVd versus Vd. The safety profile of PVd was consistent with previous reports. These data support the use of PVd as an effective treatment option in pts with RRMM.