P-217: Isatuximab plus Carfilzomib and Dexamethasone in relapsed Multiple Myeloma patients with high-risk cytogenetics: IKEMA subgroup analysis

Abstract

<h3>Background</h3> A prespecified interim efficacy analysis of Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) + carfilzomib (K) and dexamethasone (d) (Isa-Kd) significantly improved progression-free survival (PFS) compared with Kd in patients (pts) with relapsed multiple myeloma (RMM) (HR 0.531; 99% CI, 0.318–0.889; P=0.0007), with a clinically meaningful increase in minimal residual disease negativity (MRD–) (29.6% vs 13.0%) and complete response (CR) (39.7% vs 27.6%) rates, and a manageable safety profile. This subgroup analysis of IKEMA examined efficacy and safety in pts with high-risk cytogenetics [t(4;14), del(17p), and t(14;16)] and/or gain(1q21). <h3>Methods</h3> Pts with 1–3 prior lines of therapy were randomized 3:2 to receive Isa-Kd (n=179) or Kd (n=123). High-risk cytogenetics was assessed by central laboratory analysis and patients were classified as high risk if abnormalities were present in ≥1 of the following: del(17p): 50% cutoff; t(4;14) or t(14;16): 30% cutoff. In addition, assessment of gain(1q21) was prespecified as ≥3 copies: 30% cutoff; 1q21 amplification as ≥4 copies: 30% cutoff. <h3>Results</h3> Of randomized pts, 23.5% (Isa-Kd) and 25.2% (Kd) had ≥1 high-risk cytogenetic abnormality (CA); 41.9% (Isa-Kd) and 42.3% (Kd) had gain(1q21); 26.3% (Isa-Kd) and 25.2% (Kd) had isolated gain(1q21); 17.9% (Isa-Kd) and 12.2% (Kd) had 1q21 amplification. Addition of Isa to Kd improved PFS (HR; 95% CI) for pts with ≥1 high-risk CA (0.724; 0.361–1.451) and standard-risk (0.440; 0.266–0.728); pts with t(4;14) (0.549; 0.232–1.301) had a more pronounced treatment effect than pts with del(17p) (0.837; 0.281–2.496). A clear PFS benefit with Isa-Kd was seen for pts with gain(1q21) (0.569; 0.330–0.981), isolated gain(1q21) (0.462; 0.219–0.972), and 1q21 amplification (0.531; 0.150–1.878). Addition of Isa (Isa-Kd vs Kd) led to an improved depth of response for ≥very good partial response (VGPR) (73.3% vs 51.9%), MRD– (32.0% vs 13.5%), and CR (41.3% vs 25.0%) rates in pts with gain(1q21) while these rates were similar between arms in pts with high-risk CA (≥VGPR: 57.1% vs 54.8%; MRD–: 21.4% vs 22.6%; CR: 23.8% vs 22.6%). Higher percentage of pts with isolated gain(1q21) achieved ≥VGPR (80.9% vs 51.6%), MRD– (36.2% vs 9.7%), and CR (46.8% vs 22.6%) with Isa-Kd vs Kd, similar to that seen in pts with standard-risk and 1q21 amplification. Grade ≥3 treatment-emergent adverse events (TEAEs) were more common with Isa-Kd vs Kd for pts with high-risk (85.7% vs 63.3%) and gain(1q21) (80.8% vs 64.7%); incidence of serious TEAEs and TEAEs fatal during study treatment was similar in both arms for high-risk pts. <h3>Conclusions</h3> Addition of Isa to Kd improved PFS in pts with high-risk CA, and both PFS and depth of response in pts with 1q21 gain/amplification, with a manageable safety profile, consistent with the benefit noted in overall IKEMA population. Isa-Kd is a new treatment option for difficult-to-treat subgroup of pts with RMM and high-risk cytogenetics. © 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.