Final analysis of ICARIA-MM demonstrated a 6.9-month improvement in survival with Isa-Pd compared to Pd alone in RRMM patients.
Isatuximab (Isa) plus pomalidomide and dexamethasone (Pd) is approved for patients with relapsed/refractory multiple myeloma (RRMM) who have had ≥2 prior lines of therapy. This approval is based on the primary analysis of ICARIA-MM, a phase 3, randomized, multicenter, open-label study that evaluated Isa-Pd versus Pd alone in patients with RRMM. An updated overall survival (OS) analysis demonstrated improvement in OS and a manageable safety profile with Isa-Pd over Pd alone.
A total of 154 patients were assigned to Isa-Pd, while 153 patients were assigned to Pd alone. At cutoff, 10.4% of Isa-Pd patients and 2% of Pd patients were still on treatment. After a median follow-up of 52.4 months, median OS was 24.6 months with Isa-Pd versus 17.7 months with Pd alone (hazard ratio [HR], 0.776 [95% confidence interval [CI], 0.594-1.1015]; 1-sided P = .0319; significance level: P = .02). These results demonstrated a clinically meaningful 6.9-month improvement in survival with Isa-Pd compared to Pd alone. Median time to next treatment with Isa-Pd and Pd was 15.5 months and 8.9 months, respectively (HR, 0.548; 95% CI, 0.417-0.718). PFS2, which is defined as the time from randomization to progression or death on the subsequent treatment, was longer with Isa-Pd versus Pd alone: median PFS2 was 17.5 months with Isa-Pd versus 12.9 months with Pd alone (HR, 0.735; 95% CI, 0.569-0.950; log-rank P = .0091).
There was a manageable safety profile that was consistent with prior ICARIA-MM analysis. Grade ≥3 adverse events (AEs) were reported in 90.8% of the Isa-Pd group versus 75.8% of the Pd-alone group. Serious treatment-emergent AEs (TEAEs) were 73.7% with Isa-Pd versus 61.1% with Pd alone. Grade 3-4 neutropenia and thrombocytopenia occurred in 84.9% and 34.2%, respectively, of patients in the Isa-Pd group versus 71.4% and 25.2% of patients in the Pd group. The most common non-hematological TEAEs with Isa-Pd were infusion reactions in 37.5% of patients. Other common non-hematological TEAEs included upper respiratory tract infections, diarrhea, pneumonia, and bronchitis. The incidence of second primary malignancies (SPM) was higher with Isa-Pd (relative risk, 3.27; 95% CI, 0.92-11.64); however, no new cases had developed since the interim OS analysis, and SPM did not negatively impact OS.
The addition of Isa to Pd significantly improved survival, with a 6.9-month difference compared to Pd alone. Significant clinical benefit and a manageable safety profile support the use of Isa-Pd as standard of care in RRMM patients.
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