The IKEMA study (Randomized, Open Label, Multicenter Study Assessing the Clinical Benefit of Isatuximab Combined With Carfilzomib [Kyprolis®] and Dexamethasone Versus Carfilzomib With Dexamethasone in Patients With Relapse and/or Refractory Multiple Myeloma Previously Treated With 1 to 3 Prior Lines; #NCT03275285) was a randomized, open-label, multicenter phase 3 study investigating isatuximab plus carfilzomib and dexamethasone (Isa-Kd) vs Kd in patients with relapsed multiple myeloma. This subanalysis analyzed the depth of response of Isa-Kd vs Kd. The primary end point was progression-free survival (PFS); secondary end points included overall response rate, very good partial response or better (≥VGPR) rate, complete response (CR) rate, and minimal residual disease (MRD) negativity rate (assessed in patients with ≥VGPR by next-generation sequencing at a 10-5 sensitivity level). At a median follow-up of 20.7 months, deeper responses were observed in the Isa-Kd arm vs the Kd arm, with ≥VGPR 72.6% vs 56.1% and CR of 39.7% vs 27.6%, respectively. MRD negativity occurred in 53 (29.6%) of 179 patients in the Isa-Kd arm vs 16 (13.0%) of 123 patients in the Kd arm, with 20.1% (Isa-Kd, 36 of 179 patients) vs 10.6% (Kd, 13 of 123 patients) reaching MRD-negative CR status. Achieving MRD negativity resulted in better PFS in both arms. A positive PFS treatment effect was seen with Isa-Kd in both MRD-negative patients (hazard ratio, 0.578; 95% CI, 0.052-6.405) and MRD-positive patients (hazard ratio, 0.670; 95% CI, 0.452-0.993). Exploratory analysis indicates that both current CR and MRD-negative CR rates are underestimated due to M-protein interference (potential adjusted CR rate, 45.8%; potential adjusted MRD-negative CR rate, 24.0%). In conclusion, there was a clinically meaningful improvement in depth of response with Isa-Kd. The CR rate in Isa-Kd was 39.7%. Mass spectrometry suggests that the potential adjusted CR rate could reach an unprecedented 45.8% of patients treated with Isa-Kd.

Cancer Care and Haematology Unit The Tweed Hospital Tweed Heads NSW Australia

Department of Haematology Leicester Royal Infirmary University Hospitals of Leicester NHS Trust Leicester United Kingdom

Department of Haematology St Vincent's Hospital University of Melbourne Melbourne VIC Australia

Department of Hemato Oncology University Hospital Ostrava Faculty of Medicine University of Ostrava Ostrava Czech Republic

Department of Hematology Japanese Red Cross Medical Center Tokyo Japan

Department of Hematology University Hospital Bordeaux Bordeaux France

Department of Hematology University Hospital of Nantes Nantes France

Department of Medicine University of California San Francisco CA

Division of Hematology Oncology Department of Medicine Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Republic of Korea

Hematology Department Regional Hospital 1 Ekaterinburg Russia

Sanofi Cambridge MA; and

Sanofi Research and Development Chilly Mazarin France

Sanofi Research and Development Vitry Sur Seine France

Translational Genomics Research Institute City of Hope Cancer Center Phoenix AZ

Wellington Blood and Cancer Center Wellington New Zealand

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Anti-CD38 antibody therapy for patients with relapsed/refractory multiple myeloma: differential mechanisms of action and recent clinical trial outcomes

Monoclonal Antibodies and Antibody Drug Conjugates in Multiple Myeloma