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Isatuximab + Pomalidomide and Dexamethasone in Frail Patients with RRMM: ICARIA-MM Subgroup Analysis

Conference Correspondent  - ASH Highlights

The phase 3 ICARIA-MM study demonstrated the efficacy and safety of isatuximab (Isa) in combination with pomalidomide and dexamethasone (Pd; Isa-Pd) in patients with relapsed/refractory multiple myeloma (RRMM). In the total patient population, progression-free survival (PFS) was significantly improved with Isa-Pd versus Pd. In elderly patients (aged ≥75 years), PFS was 11.4 months versus 4.5 months for Isa-Pd versus Pd, respectively (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.24-0.95). The goal for this post-hoc analysis was to investigate the impact of frailty on clinical outcomes and toxicity in patients receiving Isa-Pd versus Pd, using a frailty score derived from baseline patient characteristics.

A total of 307 patients who had received ≥2 prior lines of therapy (including lenalidomide and a proteasome inhibitor) were randomized to Isa-Pd (n = 154) or Pd (n = 153). Patients in the Isa-Pd arm were initiated on intravenous Isa 10 mg/kg weekly over the first 4 weeks, and then were switched to every 2 weeks. All patients were administered recommended doses of Pd. Treatment was continued until disease progression (DP) or the emergence of unacceptable adverse events (AEs). Frailty scores at baseline were calculated based on age, modified Charlson Comorbidity Index based on medical history recorded, and Eastern Cooperative Oncology Group performance status. In cases where previous relevant medical history was absent, patients were excluded from the analysis. Patients were classified as fit (0), intermediate (1), or frail (≥2), based on their frailty score sums.

The overall study population included 28.0% frail patients (Isa-Pd, 31.2%; Pd, 24.8%) and 69.4% fit/intermediate patients. Median age in both frail and fit/intermediate patient subgroups at baseline was similar between the Isa-Pd and Pd treatment arms. Among frail patients, median PFS was 9.0 months for Isa-Pd versus 4.5 months for Pd (HR, 0.81; 95% CI, 0.45-1.48; P = .4928). For fit/intermediate patients, median PFS was 12.7 for Isa-Pd versus 7.4 months for Pd (HR, 0.49; 95% CI, 0.33-0.73; P = .0004). Median overall survival (OS) was not reached. The probability of OS at 12 months in frail patients was 66.9% (95% CI, 50.8-78.7) for Isa-Pd versus 58.8% (95% CI, 41.0-72.9) for Pd. Among fit/intermediate patients, the probability of OS at 12 months was 75.0% (95% CI, 64.5-82.8) for Isa-Pd versus 64.5% (95% CI, 53.9-73.3) for Pd. The overall response rate (ORR) in frail patients was 52.1% for Isa-Pd versus 34.2% for Pd (P = .0476). The ORR for fit/intermediate patients was 66.3% for Isa-Pd versus 35.7% for Pd (P <.0001). The rate of frail patients achieving very good partial response or better (≥VGPR) was 29.2% for Isa-Pd versus 2.6% for Pd (P = .0013). Among fit/intermediate patients, the ≥VGPR rate was 34.7% for Isa-Pd versus 10.7% for Pd (P <.0001).

Among frail patients, grade ≥3 treatment-emergent AEs (TEAEs) occurred in 91.7% of Isa-Pd patients versus 80.6% of Pd patients. Among frail patients, 8.3% of patients treated with Isa-Pd versus 16.7% of patients treated with Pd discontinued treatment because of AEs. The percentage of patients discontinuing treatment because of DP was 41.7% for Isa-Pd and 58.3% for Pd. The most common TEAEs were neutropenia (50.0% vs 38.9%), diarrhea (33.3% vs 27.8%), infusion reactions (31.3% vs 0%), upper respiratory tract infection (25.0% vs 8.3%), and bronchitis (27.1% vs 11.1%), for Isa-Pd and Pd, respectively.

For frail patients treated with Isa-Pd, tumor response, long-term treatment benefit, and safety profile were consistent with the overall ICARIA-MM study population and the elderly subgroup analysis. In addition, fewer frail patients discontinued therapy on the Isa-Pd arm versus the Pd arm. Results from this post-hoc analysis provide further support for the benefit of Isa-Pd therapy for frail patients with RRMM.


Reference

Abstract and poster 1411. ASH 2020. December 5, 2020. Isatuximab Plus Pomalidomide and Dexamethasone in Frail Patients with Relapsed/Refractory Multiple Myeloma: Icaria-MM Subgroup Analysis.

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