ISATUXIMAB PLUS CARFILZOMIB AND DEXAMETHASONE IN PATIENTS WITH RELAPSED MULTIPLE MYELOMA AND SOFT-TISSUE PLASMACYTOMAS: IKEMA SUBGROUP ANALYSIS

Abstract

Objective: Phase 3 IKEMA study (NCT03275285) showed significant improvement in PFS with Isatuximab (Isa) + carfilzomib (K) and dexamethasone (d) vs Kd in patients (pts) with relapsed multiple myeloma (MM) (HR: 0.531; 99% CI: 0.32–0.89; P=0.0007), leading to approval of Isa-Kd in US for adults with MM with 1–3 prior lines and in EU for those with ≥1 prior therapy. This post-hoc analysis evaluated efficacy and safety of Isa-Kd vs Kd in relapsed MM pts with pre-existing soft-tissue plasmacytomas (STP). Methodology: Pts (N=302) were randomized (3:2) to Isa-Kd (n=179; 12 had STP) or Kd (n=123; 7 had STP). Doses: Isa: 10 mg/kg IV QW for 4 weeks, then Q2W; K 20 mg/m² days 1–2, then 56 mg/m² twice-weekly 3 of 4 weeks; d: 20 mg twice-weekly. Independent review committee assessed response based on central radiology review and central lab M-protein using International Myeloma Working Group criteria. Median (range) duration of exposure in STP pts (Isa-Kd vs Kd) was 41.9 (2–87) vs 29.9 (4–83) weeks. Results: In STP sub-group, PFS (95% CI) improved in Isa-Kd vs Kd: HR 0.574 (0.125–2.640); median PFS was Isa-Kd: 18.76 months (4.435–not calculable [NC]) vs Kd: NC (0.986–NC). Response rates improved in Isa-Kd vs Kd: overall (50.0% vs 28.6%), ≥VGPR (33.3% vs 14.3%), CR (25.0% vs 0%, all with MRD negativity). TEAE rates (n [%]; Isa-Kd vs Kd) were: Grade ≥3: 12 (100%) vs 4 (57.1%); Grade 5: 2 (16.7%) vs 1 (14.3%); serious: 9 (75.0%) vs 4 (57.1%); discontinuation: 0 (0%) vs 1 (14.3%). Conclusion: Baseline characteristics in STP subgroup were similar to overall ITT population, except ISS stages II, III, and renal function impairment, which were more prevalent in STP subgroup vs ITT. Isa-Kd vs Kd improved PFS and depth of response in pts with relapsed MM and STP, with manageable safety profile, consistent with the benefit observed in IKEMA overall population. Isa-Kd is a new treatment option for pts with relapsed MM and STP.