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Abstracts P060

Updated Progression-free Survival (PFS) and Depth of Response in IKEMA, A Randomized Phase 3 Trial of Isatuximab, Carfilzomib and Dexamethasone (Isa-Kd) vs Kd in Relapsed Multiple Myeloma (MM)

Introduction:
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.
Methods:
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‚Äâweeks and then every 2‚Äâweeks; Kd (20/56 mg/m , twice weekly, 3/4‚Äâweeks) was administered in both arms.
Results:
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 was consistent with the IA results, which showed significant benefit in favor of Isa-Kd (vs 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. Primary PFS analysis as per FDA request/sensitivity analysis for other countries (censoring PFS event occurring >8 weeks after last valid assessment) was 41.7 vs 20.8-months (HR: 0.59, 95.4% CI: 0.42-0.83). With additional follow up and using the Hydrashift Isa immunofixation assay to rule out potential Isa interference in CR determination, final CR rate was 44.1% (95% CI: 0.37–0.52) in Isa-Kd vs 28.5% (95% CI: 0.21-0.37) (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). Addition of Isa to Kd (vs Kd) also delayed time to next treatment, with HR 0.55 (95% CI: 0.40–0.76). 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%).
Discussion:
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. The PFS analysis using FDA censoring rules showed consistent results with the IA as well. Our findings support Isa-Kd as a standard of care treatment for pts with relapsed MM.
Publisher
John Wiley & Sons; Hoboken, USA
Source Journal
American Journal of Hematology
E ISSN 1096-8652 ISSN 0361-8609