Isatuximab plus carfilzomib and dexamethasone in relapsed multiple myeloma patients with high‐risk cytogenetics: IKEMA subgroup analysis

INTRODUCTION: The presence of high‐risk chromosomal abnormalities [t(4;14), del(17p), and t(14;16)] has been linked with inferior outcomes in patients with multiple myeloma (MM). A prespecified interim analysis of the Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) + carfilzomib (K) and dexamethasone (d; Isa‐Kd) significantly improved progression‐free survival (PFS) versus Kd in patients with relapsed MM. This prespecified subgroup analysis of IKEMA examined efficacy and safety in patients with high‐risk cytogenetics. METHODS: High‐risk cytogenetics was assessed by central laboratory and patients were classified as high risk if abnormalities were present in ≥1 of the following: del(17p): 50% cutoff; t(4;14), and/or t(14;16): 30% cutoff. RESULTS: Of the randomized patients, 23.5% (Isa‐Kd) and 25.2% (Kd) had ≥1 high‐risk chromosomal abnormality. A PFS benefit was seen in favor of Isa‐Kd for patients with standard‐risk (HR 0.440; 95% CI 0.266–0.728) and high‐risk cytogenetics (HR 0.724; 95% CI 0.361–1.451). Grade ≥3 treatment‐emergent adverse events (TEAEs) were more common with Isa‐Kd (85.7%) versus Kd (63.3%) in patients with high‐risk cytogenetics; however, the incidence of serious TEAEs (64.3% vs. 66.7%) was similar. CONCLUSIONS: Isa‐Kd is a new treatment option for the difficult‐to‐treat subgroup of patients with relapsed MM and high‐risk cytogenetics.