Efficacy of High-Dose Carfilzomib in MRD-Negative Multiple Myeloma
Posted: Monday, May 10, 2021
A study conducted by Ola Landgren, MD, PhD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues assessed the efficacy of high-dose carfilzomib in patients with multiple myeloma based on their minimal residual disease (MRD, also known as measurable residual disease) status. Participants fared well on carfilzomib doses of 56 mg/m2, demonstrating effectiveness and tolerability with a consistent safety profile to that of lower doses. These results were published in a letter to the editor in the American Journal of Hematology.
This phase I/II clinical trial enrolled 28 patients who were recently diagnosed with multiple myeloma. In phase I, three participants were administered 20/45 mg/m2 (KRd-45) and six were given 20/56 mg/m2 (KRd-56) of twice-weekly carfilzomib in combination with lenalidomide and dexamethasone to evaluate dose-limiting toxicity. In phase II, the remaining 19 patients received KRd-56 with the same combination to determine the maximum tolerated dose; MRD testing was performed to assess negativity.
The median follow-up was 36.7 months. No dose-limiting toxicities occurred in phase I, but common treatment-related adverse events such as electrolyte abnormalities (34%), lymphopenia (24%), infections (24%), and cardiac events (17%) were observed.
The median number of cycles delivered to patients who achieved MRD negativity with complete response/stringent complete response status was eight; the maximum number of cycles was 12. The best responses for patients on KRd-56 were MRD-negative complete response/stringent complete response (48%), very good partial response (40%), and at least a very good partial response with MRD-negative bone marrow (60%).
Patients who achieved MRD negativity with complete response/stringent complete response had a better progression-free survival rate (89%) than other participants in the KRd-56 group (64%) at 24 months. Although median overall survival was not reached, the 36-month progression-free survival rates for KRd-56 and the combined cohorts were 73% and 77%, respectively.
Disclosure: For full disclosures of the study authors, visit onlinelibrary.wiley.com.
