Adding Daratumumab to Combination Therapy for Newly Diagnosed Multiple Myeloma
Posted: Friday, July 23, 2021
The addition of the monoclonal antibody daratumumab to weekly dosing of carfilzomib with lenalidomide and dexamethasone appeared to be associated with high rates of minimal residual disease (MRD) negativity in patients with newly diagnosed multiple myeloma. The results of the nonrandomized MANHATTAN trial were published by Neha Korde, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues in JAMA Oncology.
This study enrolled 41 patients with newly diagnosed multiple myeloma between October 2019 and November 2019. Patients were treated with eight 28-day cycles of intravenous carfilzomib; 25 mg of oral lenalidomide; 40 mg of dexamethasone; and 16 mg/kg of intravenous daratumumab.
After a median follow-up of 20.3 months from the start of treatment, MRD negativity in the bone marrow was seen in 29 of the 41 patients (71%). Patients required a median of six cycles to achieve MRD negativity. The very good partial response rate was 100%, and the complete response rate was 95%. The 1-year progression-free survival rate was 98%, and the overall survival rate was 100%. The rate of MRD achievement was similar among patients with both high-risk and standard-risk disease (odds ratio = 1.7, P = 0.5). Only 1 of the 29 patients who achieved MRD negativity had progression of disease at the time of data collection.
The most common grade 3 or 4 adverse events (seen in at least 2 patients) were neutropenia (12 patients), rash (4 patients), lung infection (3 patients), and increased alanine aminotransferase levels (2 patients). Grade 2 infusion-related reactions occurred in 18 patients (40%) during the first infusion, but no patients were reported to have had reactions during subsequent infusions. Serious adverse events were seen in eight patients (18%), the most common of which was lung infection. No patients enrolled in the trial died.
Disclosure: For full disclosure of study authors, visit jamanetwork.com.