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Phase III IKEMA Trial: Isatuximab, Carfilzomib, and Dexamethasone in Resistant Myeloma

By: Joshua Swore, PhD
Posted: Thursday, October 13, 2022

Many patients with relapsed multiple myeloma (39.7%) had a complete response to triplet therapy with the monoclonal antibody isatuximab, carfilzomib, and dexamethasone (Kd), according to an article published in Blood Advances. “IKEMA is the first phase III study to evaluate the triplet regimen...and the first to show progression-free survival and overall survival superiority over bortezomib/dexamethasone in relapsed/refractory multiple myeloma” said Thomas Martin, MD, of the University of California, San Francisco, and colleagues. “With many patients experiencing relapses following multiple therapies, there is a continual need for new molecules and novel combinations of treatments to improve patient outcomes.”

IKEMA included 302 patients with relapsed multiple myeloma. Patients were randomly divided on a 3:2 basis to receive isatuximab plus Kd or Kd alone. Next-generation sequencing and mass spectrometry were used to assess measurable residual disease (MRD) and effectiveness of both treatment arms.

At a median follow-up of 20.7 months, 72.6% of patients treated with isatuximab plus Kd had very good partial responses or better, as opposed to 56.1% of patients treated with Kd alone. With isatuximab plus Kd, MRD negativity was achieved in 29.6% of patients, compared with 20.1% with Kd alone. Those patients whose treatment resulted in MRD negativity also had better progression-free survival despite the treatment arm.

The authors suggested that current complete response rates in patients with multiple myeloma may be underestimated because of M-protein interference. Mass spectrometry was used to adjust for M-protein interference and to assess complete response. The study authors concluded: “Mass spectrometry suggests that the potential adjusted complete response rate could reach an unprecedented 45.8% of patients treated with isatuximab plus Kd.”

Disclosure: For full disclosures of the study authors, visit ashpublications.org.


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