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Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Posted: Wednesday, August 24, 2022
Andrzej J. Jakubowiak, MD, PhD, of the University of Chicago Medical Center, and colleagues aimed to determine whether a new quadruplet treatment combination for patients with newly diagnosed multiple myeloma would obviate the need for front-line autologous stem cell transplantation. Published in JAMA Oncology, the results of this phase II trial demonstrated a high rate of measurable residual disease (MRD) negativity and stringent complete response with the combination of the monoclonal antibody elotuzumab plus weekly carfilzomib, lenalidomide, and dexamethasone (KRd).
“An MRD-adapted design using dexamethasone without transplant was associated with deep, durable responses and an expected safety profile,” concluded the investigators. “This approach provides support for further evaluation of [MRD]-guided de-escalation of therapy to decrease treatment exposure while sustaining deep responses.”
This multicenter, open-label study focused on 46 newly diagnosed patients with multiple myeloma. Participants were administered 12 to 24 cycles of elotuzumab plus weekly KRd, followed by identical maintenance therapy without carfilzomib until disease progression.
The median patient age was 62, with many patients identifying as White (70%) or male (72%). A total of 22 participants were reported to have high-risk cytogenetic abnormalities. With a median treatment duration of 18 months, the rate of MRD negativity and/or stringent complete response was 58%—meeting the predetermined statistical efficacy threshold at eight cycles. Of note, both the mass spectrometry–negativity (65%) and MRD-negativity (70%) rates increased over time.
The estimated 3-year survival for patients who achieved MRD negativity was 92%. Dose reductions were reported KRd and elotuzumab in 21, 17, 16, and 1 patient, respectively; three participants discontinued treatment because of adverse events. The most frequently observed grade 3 or 4 adverse events were lung and nonpulmonary infections, and there was one case of grade 5 myocardial infarction.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
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