P-198: Isatuximab plus Carfilzomib and Dexamethasone in East Asian patients with relapsed Multiple Myeloma: IKEMA subgroup analysis

Abstract

<h3>Background</h3> Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) plus carfilzomib and dexamethasone (Kd) significantly improved progression-free survival (PFS) compared with Kd in patients (pts) with relapsed multiple myeloma (RMM) (hazard ratio [HR] 0.53; 99% confidence interval [CI] 0.32–0.89; P=0.0007). We evaluated efficacy and safety of Isa-Kd in East Asian pts (19 Japanese, 27 Korean) from IKEMA study. <h3>Methods</h3> RMM pts who received 1–3 prior lines of therapy were stratified to receive Isa-Kd or Kd. Isa-Kd arm received Isa (10 mg/kg intravenously) weekly for 4 weeks, then every 2 weeks. Both arms received K (20 mg/m2 Days 1–2, 56 mg/m2 thereafter) twice-weekly for 3 of 4 weeks, and d (20 mg) twice-weekly. Treatment continued until disease progression or unacceptable adverse events (AEs). The primary endpoint was PFS. Key secondary endpoints were overall response rate (ORR), very good partial response or better (≥VGPR), minimal residual disease negativity (MRD–), and complete response (CR) rates. Complete renal response (CRr, increase in eGFR from <50 mL/min/1.73 m2 at baseline to ≥60 mL/min/1.73 m2 in at least one post-baseline assessment) was also measured. <h3>Results</h3> East Asian pts (25 Isa-Kd, 21 Kd) were randomized. Pt characteristics were similar in the East Asian subgroup and the intent to treat (ITT) population (N=302). Median age (Isa-Kd 64.0 [range 45–83] years vs Kd 60.0 [33–73] years); median prior lines Isa-Kd 2.0 (1–3) vs Kd 1.0 (1–3); refractory to lenalidomide 16.0% Isa-Kd vs 47.6% Kd; refractory to proteasome inhibitor 20.0% Isa-Kd vs 33.3% Kd; high-risk cytogenetics 48.0% Isa-Kd vs 42.9% Kd. After a median follow-up of 20.7 months, PFS HR (0.64; 95% CI: 0.23–1.76) favored Isa-Kd, consistent with the HR in ITT population. ORR was high in both arms (Isa-Kd 88.0% vs Kd 81.0%); however, addition of Isa to Kd improved ≥VGPR (Isa-Kd 80.0% vs Kd 52.4%), MRD– (Isa-Kd 44.0% vs Kd 9.5%), and CR (Isa-Kd 44.0% vs Kd 23.8%) rates in East Asian pts, consistent with the ITT population (Isa-Kd vs Kd) (≥VGPR: 72.6% vs 56.9%; MRD–: 29.6% vs 13.0%; CR: 39.7% vs 27.6%). Renal response (CRr) was 100% (3/3 pts) in Isa-Kd vs 0% (0/2 pts) in Kd arm. Safety profile of Isa-Kd in East Asian pts was similar to the ITT population: Grade ≥3 AEs were observed in 79.2% Isa-Kd vs 55.0% Kd pts, serious TEAEs in 45.8% Isa-Kd vs 50.0% Kd pts, TEAEs fatal during study treatment in 0% Isa-Kd vs 5.0% Kd pts, and TEAEs leading to treatment discontinuation in 4.2% Isa-Kd vs 10.0% Kd pts. Overall, 64.0% Isa-Kd vs 42.9% Kd pts were still on treatment. <h3>Conclusions</h3> Efficacy and safety results of Isa-Kd in East Asian pts are consistent with overall IKEMA population; similar treatment effect for PFS, ≥VGPR, MRD–, and CR rates was reported in favor of Isa-Kd without an increase in the number of pts with serious TEAEs, TEAEs fatal during study treatment, or leading to discontinuations. Isa-Kd is a potential new treatment option for East Asian pts with RMM. © 2021 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2021 ASCO Annual Meeting. All rights reserved.