This report analyzed the depth of response of isatuximab plus carfilzomib and dexamethasone (Isa-Kd) vs Kd in relapsed multiple myeloma.
Deeper responses were observed with Isa-Kd, including a complete response rate of 39.7% (increased to 45.8% when adjusted).
The IKEMA study (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. In this subanalysis the depth of response of Isa-Kd vs Kd was analyzed. 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 10-5 sensitivity level). At a median follow-up of 20.7 months, deeper responses were observed in Isa-Kd arm vs Kd arm with ≥VGPR 72.6% vs 56.1% and CR of 39.7% vs 27.6%, respectively. MRD negativity occurred in 53/179 (29.6%) patients in Isa-Kd arm vs 16/123 (13.0%) in Kd arm with 20.1% (36/179 patients Isa-Kd) vs 10.6% (13/123 patients Kd) 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 (HR, 0.578, 95% CI, 0.052-6.405) and MRD-positive patients (HR, 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 conclusionthere was a clinically meaningful improvement in depth of response with Isa-Kd. 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 in Isa-Kd.