OA-48: Isatuximab plus Carfilzomib and Dexamethasone Versus Carfilzomib and Dexamethasone in Patients With Relapsed Multiple Myeloma (IKEMA): Final Overall Survival Analysis

Introduction: Isatuximab (Isa) is an anti-CD38 monoclonal antibody approved in combination with carfilzomib (K) and dexamethasone (d) for patients (pts) with relapsed multiple myeloma (MM) after ≥1 prior therapy, based on the primary progression-free survival (PFS) analysis of the Phase 3 IKEMA study (HR: 0.531; 99% CI: 0.318−0.889; one-sided p=0.0007; NCT03275285). At final PFS analysis 2 years later with a median follow-up of 43.96 months, the median PFS was reached — 35.65 mo (Isa-Kd) vs 19.15 mo (Kd). Here we report the final overall survival (OS) results from IKEMA planned 3 years after the primary PFS analysis.

Methods: Pts with 1−3 prior lines of therapy were randomized 3:2 to receive Isa-Kd (n=179) or Kd (n=123). Treatment was given until progressive disease, unacceptable toxicity, or pt wish. Safety was assessed in all treated pts.

Results: As of 7 February 2023 (cutoff), with a median follow-up of 56.61 mo, 42 (23.5%) and 7 (5.7%) pts in the Isa-Kd and Kd arms were still on treatment (tx); 81 (45.3%) and 66 (53.7%), respectively, discontinued due to progressive disease. Median tx duration was longer with Isa-Kd vs Kd (94.0 vs 61.9 weeks). A trend toward an OS benefit was observed with Isa-Kd vs Kd (median OS not reached [NR; 95% CI: 52.172−NR] vs 50.6 mo [95% CI: 38.932−NR]; HR: 0.855; 95% CI: 0.608−1.202; nominal one-sided p=0.1836). A sensitivity analysis censoring COVID-19 deaths showed consistent results (HR: 0.803; 95% CI: 0.564−1.142). Time to next tx (TTNT) was in favor of Isa-Kd (median 43.99 [95% CI: 31.31−NR] vs 25.0 [95% CI: 17.938−31.31] mo; HR: 0.583; 95% CI: 0.429−0.792; nominal one-sided p=0.0002), as was second progression-free survival (PFS2; median 47.18 [95% CI: 38.965−57.922] vs 32.36 [95% CI: 23.129−40.016] mo; HR: 0.663; 95% CI: 0.491−0.895; nominal one-sided p=0.0035). The difference between arms in median PFS2 (14.82 mo) remains very close to the difference in median PFS (16.50 mo). More pts in the Kd vs Isa-Kd arm received further anti-myeloma therapies that included those with novel mechanisms of action (MoA; 65.9% vs 49.7%) and further anti-CD38 agents (63.0% vs 29.2%). The safety profiles of both arms were comparable to those in the interim and final PFS analyses. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 84.2% (Isa-Kd) and 73.0% (Kd) of pts, while serious TEAEs occurred in 71.2% and 60.7% of pts. TEAEs leading to tx discontinuation occurred in 13.6% Isa-Kd and 18.0% Kd pts. Despite longer exposure, both arms had a similar incidence of cardiac failure (Isa-Kd: 8.5%; Kd: 8.2%).

Conclusions: This final OS analysis shows a meaningful trend for OS benefit with Isa-Kd vs Kd despite subsequent tx with anti-CD38 agents, introduction of tx with novel MoA among further therapies, and the COVID-19 pandemic. Improvements in TTNT and PFS2 were observed, and sustained PFS benefit still observed at PFS2. The Isa-Kd safety profile was consistent with previous analyses, supporting it as a standard-of-care therapy for relapsed MM pts.

Funding: Sanofi.