UPDATED PROGRESSION-FREE SURVIVAL AND DEPTH OF RESPONSE IN IKEMA, A RANDOMIZED PHASE 3 TRIAL OF ISATUXIMAB, CARFILZOMIB AND DEXAMETHASONE VS CARFILZOMIB AND DEXAMETHASONE IN RELAPSED MULTIPLE MYELOMA

Abstract

The anti-CD38 antibody Isa in combination with Kd is approved in various countries for patients (pts) with relapsed MM after ≥1 prior therapy, based on primary interim analysis (IA) of the Phase 3 IKEMA study (NCT03275285). Here we report updated efficacy and safety results from IKEMA. This prespecified final analysis (179 pts randomized to Isa-Kd, 123 to Kd) evaluated updated PFS (primary endpoint), PFS2, minimal residual disease negativity (MRD-) rate, complete response (CR) rate, MRD- and CR rate in ITT population, and safety with 2 additional years of follow-up. Isa 10 mg/kg was given IV weekly for 4 wks and then every 2 wks; Kd (20/56 mg/m 2 , twice weekly, 3/4 weeks) was administered in both arms. At cutoff (14-Jan-2022) with a median (m) follow-up of 44-months, 49 (27.4%) pts in Isa-Kd and 11 (8.9%) in Kd were still on treatment. The updated PFS update was consistent with the IA results, showing significant benefit in favor of Isa-Kd: HR 0.58 (95.4% CI 0.42–0.79) with median (m) PFS 35.7 mo (95% CI: 25.8-44.0) vs 19.2 mo (95% CI: 15.8-25.0) in Isa-Kd vs Kd. PFS2 HR was 0.68 (95% CI 0.50–0.94) with mPFS2 47.2 mo (95% CI: 38.1-NC) vs 35.6 mo (95% CI: 24.0-40.5) in Isa-Kd vs Kd. With additional follow up and using the Hydrashift Isa immunofixation assay to rule out potential Isa interference in CR determination, final CR rate (Isa-Kd vs Kd) was 44.1% (95% CI: 0.37–0.52) vs 28.5% (95% CI: 20.7–37.3) (OR = 2.09, 95%CI = 1.26–3.48); ORR was 86.6% (95% CI: 0.81–0.91) vs 83.7% (95% CI: 0.76–0.90); MRD- was reached in 33.5% (95% CI: 0.27–0.41) vs 15.4% (95% CI: 0.10–0.23) pts (OR = 2.78, 95%CI = 1.55–4.99); rate of MRD- CR pts was 26.3% (95% CI: 0.20–0.33) vs 12.2% (95% CI: 0.07–0.19) (OR = 2.57, 95%CI=1.35–4.88). Safety profiles in both arms remain consistent with prior IKEMA findings. Serious TEAEs were reported in 70.1% of Isa-Kd pts vs 59.8% in Kd. The most common, any-grade non-hematologic TEAEs in Isa-Kd were infusion reaction (45.8%), diarrhea (39.5%), hypertension (37.9%) and upper respiratory tract infection (37.3%). These results show unprecedented mPFS, CR rate, MRD- and MRD- CR rates in a non-lenalidomide containing regimen with benefit maintained through subsequent therapies and a manageable safety profile. Our findings support Isa-Kd as a standard of care treatment for pts with relapsed MM. Study funded by Sanofi. Philippe Moreau and Thomas Martin are Co-primary investigators. Abstract previously presented at ESMO/COMy 2022.