Multiple Myeloma Coverage from Every Angle

Carfilzomib-Based Therapy for High-Risk Smoldering Multiple Myeloma

By: Melissa Steele-Ogus
Posted: Thursday, January 14, 2021

Without treatment, 75% of patients with high-risk smoldering multiple myeloma may progress to symptomatic multiple myeloma within 5 years. In 2015, a pilot study investigated the efficacy of carfilzomib, lenalidomide, and dexamethasone (KRd) followed by lenalidomide maintenance in this patient population. At 5-year follow-up, just 10% of treated patients developed multiple myeloma. The results from the second phase of this study, led by Dickran Kazandjian, MD, of the NIH’s Center for Cancer Research Multiple Myeloma Program, were presented during the 2020 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 548).

“Overall, the benefit compared to risk with KRd in smoldering multiple myeloma is very favorable. Future randomized trials will be needed to lock in this conclusion,” the investigators commented.

This phase II study had a single-arm, enrolling patients with high-risk smoldering multiple myeloma, all of whom received the treatment. Treatment consisted of eight 28-day cycles of KRd. Patients then received maintenance therapy, consisting of oral lenalidomide for 24 cycles.

A total of 52 patients were enrolled in the study, with a median follow-up of 27.3 months. Median residual disease–negative (MRD) complete remission rate was 70.2%, and the MRD-negative very good response rate was 80.9%. Two and four patients progressed to symptomatic or biochemical multiple myeloma, respectively. No patients died. The overall rate of response was 100%, and 78% achieved a best response of stringent complete remission. Grade 3 or 4 toxicities occurred in 33% of patients, the most common of which included neutropenia, lymphopenia, and thromboembolism. A total of four patients discontinued treatment, three due to toxicities, and one patient withdrew from the study.

Disclosure: For full disclosures of the study authors, visit

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