In a literature review published in the journal Cureus, researchers characterized the efficacy and safety of daratumumab as a component of combination therapy for treatment of relapsed/refractory multiple myeloma (RRMM). The review was conducted by Anusha Bapatla, MD, of Sinai Grace Hospital in Detroit, Michigan, and the California Institute of Behavioral Neuroscience & Psychology in Fairfield, CA, and colleagues.
The monoclonal antibody daratumumab has been approved by the US Food and Drug Administration in treatment of RRMM. However, Dr Bapatla and colleagues explained that while studies have evaluated the use of daratumumab as a component of combination therapy for RRMM, research on the role of daratumumab remains limited.
In this study, the researchers performed searches of PubMed, Medline, PubMed Central, and Research Gate databases for literature from the prior 5 years that pertained to RRMM, monoclonal antibodies, daratumumab, and novel agents. Included trials were written in the English language and were available as free full-text publications.
The literature search yielded 21 relevant publications. In the POLLUX and CASTOR trials, the addition of daratumumab to combination therapies was typically associated with improvements in progression-free survival, including at extended follow-ups. Greater efficacy was also seen in a prolonged follow-up of the POLLUX trial in patients with cytogenetic risk factors when daratumumab was added to the combination of lenalidomide with dexamethasone.
In an extended follow-up of the CASTOR trial, the overall response rate showed significant improvement, including in patients with cytogenetic risk factors, when daratumumab was added to the combination of bortezomib and dexamethasone. The researchers additionally detailed promising safety and efficacy results in early-phase studies when daratumumab was added to other combinations.
Regarding safety, the CASTOR trial showed more adverse events (AEs) at interim analysis in the treatment arm containing daratumumab, but AE-related discontinuation rates were similar across treatment arms. In the POLLUX study, treatment arms with or without daratumumab experienced similar rates of AEs. With extended follow-up in that study, Dr Bapatla and colleagues noted, the arm receiving daratumumab showed higher rates of AEs, but with a low level of discontinuations.
Dr Bapatla and colleagues noted in their review that limited information appeared to be available regarding the use of daratumumab-containing combination regimens in patients with end-stage kidney disease. They recommended that more randomized controlled trials be conducted to evaluate daratumumab in combination therapies for patients with this condition.
Bapatla A, Kaul A, Dhalla PS, et al. Role of daratumumab in combination with standard therapies in patients with relapsed and refractory multiple myeloma. Cureus. 2021;13(6):e15440. doi:10.7759/cureus.15440