Isatuximab Combination Produced Deep Responses in Relapsed Multiple Myeloma

By Leah Lawrence - Last Updated: November 22, 2022

Treatment of relapsed multiple myeloma (MM) with the combination of isatuximab plus carfilzomib and dexamethasone (Isa-Kd) resulted in clinically improved depth of response compared with Kd alone, according to results of the IKEMA study.

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“The high incidence of patients with at least 1 prior line of treatment reaching minimal residual disease (MRD)-negative complete response in the Isa-Kd arm further supports Isa-Kd as a new standard treatment for patients with relapsed MM,” study researchers wrote.

In IKEMA, patients with relapsed disease who received one to three prior lines of therapy were randomized 3:2 to receive Isa-Kd or Kd. At a prespecified interim analysis, with a median follow-up of 20.7 months, the median progression-free survival (PFS) was not reached for Isa-Kd compared with 19.2 months for Kd (hazard ratio [HR]=0.531; 99% CI, 0.318-0.889; one-side P=.0007).

At the positive PFS interim analysis, patients assigned to Isa-Kd had deeper responses compared with Kd. The rate of very good partial response or better was 72.6% for Isa-Kd compared with 56.1% for Kd. The rate of complete response or better was 39.7% for Isa-Kd compared with 27.6% for Kd alone.

The researchers also found that MRD-negativity occurred in 29.6% of patients assigned to Isa-Kd compared with 13.0% of patients assigned to Kd.

Positive PFS treatment effect was seen with Isa-Kd in both MRD-negative (HR=0.578; 95% CI, 0.052-6.405) and MRD-positive patients (HR=0.670; 95% CI, 0.452-0.993).

“Recent recommendations from the International Myeloma Working Group (IMWG) Mass Spectrometry Committee have endorsed the use of mass spectrometry to aid in distinguishing therapeutic antibodies from endogenous M-protein,” the researchers wrote. “While mass spectrometry has not yet been incorporated in the IMWG response criteria, the mass spectrometry results in the IKEMA study suggest that conventional disease assessments using immunofixation have led to an approximate 6% underestimation of complete response (CR) rate (adjusted CR rate 45.8%) and an approximately 4% underestimation of MRD-negative CR rate (adjusted MRD-negative CR rate 24%) in the Isa-Kd arm.”

Martin TG, Mikhael J, Hajek R, et al. Depth of response and response kinetics of isatuximab plus carfilzomib and dexamethasone in relapsed multiple myeloma. Blood Adv. 2022. doi:10.1182/bloodadvances.2021006713

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