A treatment regimen for multiple myeloma (MM) that combines daratumumab with lenalidomide and dexamethasone “significantly extended” overall survival (OS) compared with lenalidomide and dexamethasone, according to the final analysis of the phase II POLLUX study.
The triplet added more than a year to the median OS, reported a research team led by Meletios Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.
“To our knowledge, for the first time, our findings, together with the OS benefit observed with daratumumab plus bortezomib and dexamethasone in the phase III CASTOR trial, demonstrate OS improvement with daratumumab-containing regimens in [relapsed or refractory MM],” the authors wrote in an article published in the Journal of Clinical Oncology.
In the multicenter, open-label study, eligible patients with MM who had at least one line of prior therapy were randomly assigned to receive daratumumab in combination with lenalidomide and dexamethasone or lenalidomide and dexamethasone alone. Patients who had positive primary analysis receiving lenalidomide and dexamethasone were also offered daratumumab monotherapy after their disease progressed.
Initial results from POLLUX had showed that daratumumab in combination with lenalidomide and dexamethasone produced a significantly longer progression-free survival at a median follow-up of 13.5 months. In their study, Dr. Dimopoulos and colleagues sought to update efficacy and safety results in final analysis of the POLLUX data.
At a median follow-up of 79.7 months, patients who received daratumumab in combination with lenalidomide and dexamethasone showed a “significant OS benefit” compared with those who received lenalidomide and dexamethasone (hazard ratio, 0.73; 95% CI, 0.58-0.91; P=.0044).
In addition, patients who were given daratumumab in combination with lenalidomide and dexamethasone had a median OS of 67.6 months, compared with 51.8 months for lenalidomide and dexamethasone only.
Delving further into the data, the researchers found that daratumumab in combination with lenalidomide and dexamethasone provided greater OS in most subgroups, including those at least 65 years old and patients with one, two, or three prior lines of therapy. This benefit was also observed in those with International Staging System stage III disease, high-risk cytogenetic abnormalities, and refractoriness to their last prior line of therapy or a proteasome inhibitor, according to the authors.
“Given the high attrition rates observed in real-world studies in Europe and the United States and the observed OS benefits with daratumumab-containing regimens in both [newly diagnosed MM] (ALCYONE and MAIA) and now [relapsed or refractory MM] (POLLUX and CASTOR), early use of daratumumab should be considered [a standard of care] to achieve deep and sustained responses and prolonged disease control,” they wrote.
Dimopoulos MA, Oriol A, Nahi H, et al. Overall survival with daratumumab, lenalidomide, and dexamethasone in previously treated multiple myeloma (POLLUX): A randomized, open-label, phase III trial. J Clin Oncol. 2023;41(8):1590-1599. doi:10.1200/JCO.22.00940