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MM-064 Updated Progression-Free Survival and Depth of Response in IKEMA, a Randomized Phase 3 Trial of Isatuximab, Carfilzomib, and Dexamethasone (Isa-Kd) Versus Kd in Relapsed Multiple Myeloma

T. Martin, MA. Dimopoulos, J. Mikhael, K. Yong, M. Capra, T. Facon, R. Hajek, I. Špička, F. Casca, S. Macé, ML. Risse, P. Moreau

. 2022 ; 22 Suppl 2 (-) : S403-S404. [pub] -

Language English Country United States

Document type Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial

Persistent link   https://www.medvik.cz/link/bmc22024245

CONTEXT: Anti-CD38 antibody Isa in combination with Kd is approved in various countries for relapsed multiple myeloma (MM) patients after ≥1 prior therapy based on primary interim analysis (IA) of the Phase 3 IKEMA study (NCT03275285). OBJECTIVE: To report updated efficacy and safety results from IKEMA. Setting and Main Outcome Measures: This prespecified analysis (179 patients randomized to Isa-Kd, 123 to Kd) evaluated progression-free survival (PFS) (primary endpoint) at 159 PFS events, PFS2, minimal residual disease negativity (MRD-) rate, complete response (CR) rate, MRD- and CR rates in all patients, and safety. INTERVENTIONS: Isa 10 mg/kg was given IV weekly for 4 weeks and then every 2 weeks; Kd (20/56 mg/m2, twice weekly, 3/4 weeks) was administered in both arms. RESULTS: At cutoff (14-Jan-2022), with a 44-month median follow-up, 49 (27.4%) patients in Isa-Kd and 11 (8.9%) in Kd were still on treatment. Updated PFS, consistent with IA results, demonstrated significant benefit in favor of Isa-Kd (vs. Kd): HR=0.58 (95.4%CI=0.42-0.79; 35.7 vs. 19.2 months); PFS2 HR=0.68 (95%CI=0.50-0.94; 47.2 vs. 35.6 months). Primary PFS analysis, per FDA request/sensitivity analysis for other countries (censoring PFS events occurring >8 weeks after last valid assessment), was 41.7 versus 20.8 months (HR=0.59, 95%CI=0.42-0.83). With additional follow-up and using Hydrashift Isa immunofixation assay to rule out potential Isa interference in CR determination, final CR rate (Isa-Kd vs. Kd) was 44.1% versus 28.5% (OR=2.09, 95%CI=1.26-3.48); ORR was 86.6% versus 83.7%; MRD- was reached in 33.5% versus 15.4% patients (OR=2.78, 95%CI=1.55-4.99); and the rate of MRD- CR patients was 26.3% versus 12.2% (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 versus 59.8% Kd patients. 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%). CONCLUSIONS: These results show unprecedented mPFS, CR, MRD-, and MRD- CR rates in non-lenalidomide containing regimens with benefits maintained through subsequent therapies and a manageable safety profile. Moreover, PFS analysis using FDA censoring rules showed consistent results with the IA. Our findings support Isa-Kd as a standard-of-care treatment for relapsed MM patients.

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$a MM-064 Updated Progression-Free Survival and Depth of Response in IKEMA, a Randomized Phase 3 Trial of Isatuximab, Carfilzomib, and Dexamethasone (Isa-Kd) Versus Kd in Relapsed Multiple Myeloma / $c T. Martin, MA. Dimopoulos, J. Mikhael, K. Yong, M. Capra, T. Facon, R. Hajek, I. Špička, F. Casca, S. Macé, ML. Risse, P. Moreau
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$a CONTEXT: Anti-CD38 antibody Isa in combination with Kd is approved in various countries for relapsed multiple myeloma (MM) patients after ≥1 prior therapy based on primary interim analysis (IA) of the Phase 3 IKEMA study (NCT03275285). OBJECTIVE: To report updated efficacy and safety results from IKEMA. Setting and Main Outcome Measures: This prespecified analysis (179 patients randomized to Isa-Kd, 123 to Kd) evaluated progression-free survival (PFS) (primary endpoint) at 159 PFS events, PFS2, minimal residual disease negativity (MRD-) rate, complete response (CR) rate, MRD- and CR rates in all patients, and safety. INTERVENTIONS: Isa 10 mg/kg was given IV weekly for 4 weeks and then every 2 weeks; Kd (20/56 mg/m2, twice weekly, 3/4 weeks) was administered in both arms. RESULTS: At cutoff (14-Jan-2022), with a 44-month median follow-up, 49 (27.4%) patients in Isa-Kd and 11 (8.9%) in Kd were still on treatment. Updated PFS, consistent with IA results, demonstrated significant benefit in favor of Isa-Kd (vs. Kd): HR=0.58 (95.4%CI=0.42-0.79; 35.7 vs. 19.2 months); PFS2 HR=0.68 (95%CI=0.50-0.94; 47.2 vs. 35.6 months). Primary PFS analysis, per FDA request/sensitivity analysis for other countries (censoring PFS events occurring >8 weeks after last valid assessment), was 41.7 versus 20.8 months (HR=0.59, 95%CI=0.42-0.83). With additional follow-up and using Hydrashift Isa immunofixation assay to rule out potential Isa interference in CR determination, final CR rate (Isa-Kd vs. Kd) was 44.1% versus 28.5% (OR=2.09, 95%CI=1.26-3.48); ORR was 86.6% versus 83.7%; MRD- was reached in 33.5% versus 15.4% patients (OR=2.78, 95%CI=1.55-4.99); and the rate of MRD- CR patients was 26.3% versus 12.2% (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 versus 59.8% Kd patients. 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%). CONCLUSIONS: These results show unprecedented mPFS, CR, MRD-, and MRD- CR rates in non-lenalidomide containing regimens with benefits maintained through subsequent therapies and a manageable safety profile. Moreover, PFS analysis using FDA censoring rules showed consistent results with the IA. Our findings support Isa-Kd as a standard-of-care treatment for relapsed MM patients.
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$a Dimopoulos, Meletios-Athanasios $u Department of Clinical Therapeutics, The National and Kapodistrian University of Athens, Athens, Greece
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$a Yong, Kwee $u Department of Hematology, University College Hospital, London, United Kingdom
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$a Facon, Thierry $u Department of Hematology, Lille University Hospital, Lille, France
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$a Hajek, Roman $u Department of Hematooncology, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
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$a Špička, Ivan $u 1st Department of Medicine, Department of Hematology, 1st Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic
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