IKEMA is an ongoing, phase 3, randomized, open-label, parallel-group study that reached its interim analysis milestone. The study evaluated the effect of adding isatuximab (Isa) to carfilzomib and dexamethasone (Kd) in patients with relapsed/refractory multiple myeloma (RRMM).
The study examines the efficacy of Isa + Kd and its impact on prolonging progression-free survival (PFS) compared with Kd alone, its primary end point. Assessment of overall response rate (ORR), very good partial response or better (≥VGPR), complete response (CR), and minimal residual disease (MRD) negativity, as well as overall survival (OS) in both treatment arms of the study, and safety were secondary outcome measures.
A total of 302 patients were enrolled in the study and randomized to 2 treatment arms: 179 patients in the Isa-Kd arm and 123 patients in the Kd arm. Eligibility criteria included patients who had undergone 1 to 3 prior lines of treatment, of which 93% had prior proteasome inhibitor therapy in the Isa-Kd group and 85% in the Kd group; 76% had prior immunomodulatory drug therapy in the Isa-Kd group and 81% in the Kd group. Patients could not have had previous exposure to carfilzomib and could not have been refractory to treatment with an anti-CD38 monoclonal antibody. The baseline patient characteristics were similar in both arms; median age was 64 years (range, 33-90 years), and 25.8% had stage 1 disease, 59.6% had stage 2 disease, and 7.9% had stage 3 disease. In addition, 24% of patients had high-risk cytogenetics. Patients were assigned randomly in a 3:2 ratio and stratified based on their International Staging System stage and the number of prior treatments in either the Isa-Kd or Kd arm. Therapy was administered in 28-day cycles; patients in the Isa-Kd arm received isatuximab 10 mg/kg intravenously weekly for 4 weeks, then every other week, and patients in both the Isa-Kd and Kd arms received carfilzomib 20 mg/m2 on days 1 and 2, and all subsequent doses at 56 mg/m2 twice weekly for 3 of 4 weeks, and dexamethasone 20 mg twice weekly. Patients continued treatment unless they experienced disease progression or intolerable adverse events.
At the time of the study’s interim analysis, median PFS rates were not reached in the Isa-Kd group and 19.2 months in the Kd group; Isa-Kd resulted in a 47% risk reduction in progression or death versus Kd (P = .0007). The PFS benefit was seen across nearly every subgroup. Not significantly different were the ORR rates (≥partial response) between the 2 arms at 86.6% for Isa-Kd and 82.9% for Kd. The ≥VGPR rates were significantly better in the Isa-Kd group versus the Kd group (72.6% vs 56.1%, respectively; P = .001). The CR rates were 39.7% and 27.6% in the Isa-Kd versus Kd arms, respectively. The MRD-negativity rates were significantly better in patients in the Isa-Kd arm versus those in the Kd arm (29.6% vs 13.0%, respectively; P = .0004). The time to next treatment was significantly delayed for patients in the Isa-Kd arm. OS was immature at the time of analysis; 17.3% of patients in the Isa-Kd arm and 20.3% in the Kd arm were recorded as dead at the time of the analysis. Median duration of follow-up was 20.7 months. However, the study is ongoing.
Unless they experienced disease progression or intolerable adverse events, patients continued treatment; 52.0% and 30.9% of patients in the Isa-Kd and Kd arms, respectively, remain on treatment. Reasons for discontinuation of treatment included progression of disease in 29.1% and 39.8% of patients in the Isa-Kd and Kd arms, respectively, or unacceptable adverse events that affected 8.5% and 13.9% of patients in the Isa-Kd and Kd arms, respectively. Grade ≥3 adverse events were reported in 76.8% and 67.2% of patients in the Isa-Kd and Kd groups, respectively. Serious adverse events in patients in the Isa-Kd arm were reported in 59.3% and 57.4% of those in the Kd arm, and fatal adverse event rates were similar in both arms at 3.4% and 3.3%, respectively. Grade ≥3 adverse respiratory events were reported in 32.2% and 23.8% of patients in the Isa-Kd and Kd arms, respectively. Grade ≥3 cardiac failure was seen in 4.0% and 4.1% of patients in the Isa-Kd–treated and Kd-treated arms, respectively; grade 3/4 thrombocytopenia was noted in 29.9% versus 23.8% and grade 3/4 in 19.2% versus 7.4% of patients treated with Isa-Kd versus Kd, respectively.
Interim results of the IKEMA study show treatment of relapsed multiple myeloma with the addition of Isa to Kd leads to a clear improvement in PFS with a tolerable safety profile. Final results are currently pending.
Reference
Abstract and Oral Presentation LB2603. EHA 2020. June 12, 2020. Isatuximab plus carfilzomib and dexamethasone in relapsed/refractory multiple myeloma (IKEMA) interim analysis of a phase 3, randomized, open-label study.