Daratumumab with bortezomib and dexamethasone significantly increased the overall survival in patients suffering from relapsed or refractory multiple myeloma.
Daratumumab is a human monoclonal CD38 antibody that poses greater cytotoxicity against multiple myeloma cells than other CD38 antibodies. Adding this drug to the standard treatment regimen for multiple myeloma significantly improves the durability of response and reduces the risk of progression of the disease. This randomized controlled trial assessed the safety and efficacy of daratumumab with bortezomib and dexamethasone (D-Vd) in the final overall survival analysis at the time of follow-up. The results, published in the Journal of Clinical Oncology, indicate that D-Vd significantly increases overall survival in relapsed or refractory multiple myeloma (RRMM) patients.
Baseline Characteristics of Study Participants
In this study, 498 patients were randomized to daratumumab, bortezomib, and dexamethasone (D-Vd) or dexamethasone only (Vd) groups. The median age of the patients was 64 years and the number of previous line therapies was 2, consisting of lenalidomide, bortezomib, and thalidomide, and both an immunomodulatory and proteasome inhibitor drug.
Efficacy of Daratumumab with Bortezomib and Dexamethasone
At the median follow-up of patients enrolled in the clinical trial at 72.6 months, 59.0% and 69.2% of patients in the D-Vd and Vd groups, respectively, had died. The D-Vd group patients demonstrated a reduction of 26% in the risk of death. The median overall survival (OS) of D-Vd and Vd patients was 49.6 and 38.5 months, respectively. Subgroup analysis demonstrated an OS benefit of D-Vd patients with advanced-stage disease, age ≥ 65 years, and prior lines of therapy. The minimal residual disease-negativity rates were significantly higher in the D-Vd group, which was associated with improved OS.
Safety of Daratumumab With Bortezomib and Dexamethasone
No new safety concerns were reported during the OS analysis at the longer follow-up. Treatment-emergent adverse events (TEAEs) of grade 3/4 included anemia, thrombocytopenia, lymphopenia, pneumonia, and neutropenia. Serious TEAEs occurred in 55.1% of D-Vd vs. 34.2% of Vd patients, and grade 3/4 infections occurred in 29.6% of D-Vd vs 19.0% of Vd patients. TEAEs that culminated to death were recorded for 7.0% of D-Vd vs 5.9% of Vd patients.
The study outcomes indicate that D-Vd treatment significantly improved overall survival in RRMM patients, particularly those with a previous line of therapy.
Sonneveld, P., Chanan-Khan, A., Weisel, K., Nooka, A. K., Masszi, T., Beksac, M., Spicka, I., Hungria, V., Munder, M., Mateos, M., Mark, T. M., Levin, M., Ahmadi, T., Qin, X., Mayo, W. G., Gai, X., Carey, J., Carson, R., & Spencer, A. (2022). Overall Survival With Daratumumab, Bortezomib, and Dexamethasone in Previously Treated Multiple Myeloma (CASTOR): A Randomized, Open-Label, Phase III Trial. Journal of Clinical Oncology, 41(8), 1600–1609. https://doi.org/10.1200/jco.21.02734