KEY TAKEAWAYS
- The phase 3 IKEMA study evaluated Isatuximab (Isa) in combination with Carfilzomib (K) and Dexamethasone (d) vs. Carfilzomib (K) and Dexamethasone (d) for the treatment of relapsed multiple myeloma (MM) patients after at least one prior therapy.
- The final analysis of overall survival (OS) suggested that Isa-Kd offers potential benefits over Kd.
In the Phase 3 IKEMA trial, relapsed multiple myeloma (MM) patients (pts) with 1 to 3 prior treatments were randomized in a 3:2 ratio to receive either Isatuximab (Isa) with Carfilzomib (K) and Dexamethasone (d) [Isa-Kd (n=179)] or Carfilzomib (K) and Dexamethasone (d) [Kd (n=123)]. The regimen continued until disease progression, intolerable side effects, or patient preference led to cessation. Safety metrics were compiled for all treated pts.
As of the cutoff date on February 7, 2023, with an average follow-up duration of 56.61 months, 42 pts (23.5%) in the Isa-Kd group and 7 pts (5.7%) in the Kd group remained on treatment. In contrast, 81 pts (45.3%) in the Isa-Kd group and 66 pts (53.7%) in the Kd group stopped treatment due to disease progression. Isa-Kd had a longer median treatment span compared to Kd, with durations of 94.0 and 61.9 weeks, respectively. While the median overall survival (OS) had not yet been reached for the Isa-Kd group, a promising trend was noted, supported by a Hazard Ratio (HR) of 0.855 (95% Confidence Interval [CI]: 0.608–1.202; one-sided p-value: 0.1836).
Similar results were found when accounting for COVID-19-related deaths (HR: 0.803; 95% CI: 0.564–1.142). Time to the next treatment (TTNT) and the second progression-free survival (PFS2) favored Isa-Kd, showing statistical significance. The gap in median PFS2 between the two groups (14.82 months) was similar to the initial difference in median PFS (16.50 months). A higher percentage of pts in the Kd group resorted to additional anti-myeloma treatments, including those with novel mechanisms of action (65.9% vs 49.7%) and further anti-CD38 agents (63.0% vs 29.2%).
The safety data for both groups aligned with earlier PFS analyses. High-grade (≥3) treatment-emergent adverse events (TEAEs) were reported in 84.2% of Isa-Kd and 73.0% of Kd pts. Serious TEAEs were present in 71.2% and 60.7% of pts in Isa-Kd and Kd groups, respectively. Discontinuation due to TEAEs was observed in 13.6% of the Isa-Kd group and 18.0% of the Kd group. Despite longer treatment durations, cardiac failure rates were similar between Isa-Kd (8.5%) and Kd (8.2%).
The final OS analysis suggested a meaningful trend in OS benefit with Isa-Kd compared to Kd, even with the use of subsequent therapies involving anti-CD38 agents or therapies with new mechanisms of action and during the COVID-19 pandemic. TTNT and PFS2 also demonstrated improvements, reinforcing Isa-Kd as a standard-of-care option for pts with relapsed MM.
Source: https://imsannual2023.eventscribe.net/fsPopup.asp?PresentationID=1302329&mode=presInfo
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03275285
Moreau, P. OA-48: Isatuximab plus Carfilzomib and Dexamethasone Versus Carfilzomib and Dexamethasone in Patients With Relapsed Multiple Myeloma (IKEMA): Final Overall Survival Analysis.
