Isatuximab plus carfilzomib and dexamethasone led to a higher MRD negativity rate and more complete responses (CR) than carfilzomib and dexamethasone in patients with relapsed/refractory (R/R) multiple myeloma (MM), according to a recent study.
Thomas Martin, MD, of the University of California, San Francisco, and colleagues conducted the study, which was a subanalysis of the randomized, open label, multicenter, phase III IKEMA study. Investigators published the results in Blood Advances.
The study included patients with R/R MM who were previously treated with one to three prior lines of therapy. The subanalysis compared the depth of response between patients treated with isatuximab plus carfilzomib and dexamethasone and patients who were treated with carfilzomib and dexamethasone. The primary endpoint of the study was progression-free survival (PFS), with secondary endpoints including the rate of “very good” or better partial response, the CR rate, and minimal residual disease (MRD) negativity rate. The median follow-up was 20.7 months.
Response rates earlier, better with isatuximab plus carfilzomib and dexamethasone
The CR rate was 39.7% in the isatuximab plus carfilzomib and dexamethasone treatment arm, compared with 27.6% in the carfilzomib and dexamethasone treatment arm. The median time to the first CR was 184 days in the isatuximab plus carfilzomib and dexamethasone treatment arm and was 229.5 days in the carfilzomib and dexamethasone treatment arm.
The “very good” or better partial response rate was 72.6% in the isatuximab plus carfilzomib and dexamethasone treatment arm, compared with 56.1% in the carfilzomib and dexamethasone treatment arm (nominal P=.0011).
MRD negativity rates higher with isatuximab plus carfilzomib and dexamethasone
MRD negativity was reported in 29.6% of patients in the isatuximab plus carfilzomib and dexamethasone treatment arm, and in 13% of patients in the carfilzomib and dexamethasone treatment arm (nominal P=.0004). MRD-negative CR was reported in 20.1% of patients in the isatuximab plus carfilzomib and dexamethasone treatment arm, and in 10.6% of patients in the carfilzomib and dexamethasone arm.
MRD negativity led to longer PFS in both treatment arms. A positive PFS treatment effect was reported in the isatuximab plus carfilzomib and dexamethasone treatment arm, in both MRD-negative (hazard ratio [HR], 0.578; 95% CI, 0.052-6.405) and MRD-positive patients (HR, 0.670; 95% CI, 0.452-0.993).
An exploratory analysis using high-resolution mass spectrometry preceded by immunocapture and liquid chromatography indicated that CR rates and MRD-negative CR rates were both underestimated due to M-protein interference (potential adjusted CR rate, 45.8%; potential adjusted MRD-negative CR rate, 24.0%).
“The mass spectrometry results suggest that the potential adjusted CR rate in patients receiving [isatuximab plus carfilzomib and dexamethasone] could reach an unprecedented 45.8% of patients previously treated with 1 to 3 prior lines of therapy,” the investigators wrote.
The results of the subanalysis show that MRD-negativity can be reached “independently of bad prognosis” in patients with MM through treatment with isatuximab plus carfilzomib and dexamethasone, the researchers reported.
“The high incidence of patients with at least 1 prior line of treatment reaching MRD-negative CR in the [isatuximab plus carfilzomib and dexamethasone] arm further supports [isatuximab plus carfilzomib and dexamethasone] as a new standard treatment for patients with relapsed MM,” the authors concluded.
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