Daratumumab Plus Lenalidomide and Dexamethasone Among Patients With R/R MM

Results from the Phase 3 POLLUX Trial

According to findings from a phase 3 study recently published in the Journal of Clinical Oncology, daratumumab plus lenalidomide and dexamethasone treatment resulted in improved overall survival among patients with relapsed/refractory (R/R) multiple myeloma (MM) compared to lenalidomide and dexamethasone alone. 

Dr Meletios A. Dimopoulos, MD, University of Athens School of Medicine, Athens, Greece, and coauthors aimed to evaluate the primary endpoint of progression-free survival (PFS) and the secondary endpoints of overall survival (OS), overall response rate, duration of response, time to response, time to progression, and safety in this multicenter, randomized, phase 3 study. 

569 patients with a median age of 65 years, R/R MM, and at least one line of prior therapy were randomized 1:1 to receive either lenalidomide and dexamethasone treatment alone (n=283), or daratumumab plus lenalidomide and dexamethasone (n=286). Both arms received 28-day cycles of lenalidomide (25 mg once daily on days 1 to 21 of each cycle and 10 mg once daily if the creatinine clearance was 30 to 60 mL/min) and dexamethasone (40 mg once weekly) until disease progression or unacceptable toxicity was observed. The daratumumab plus lenalidomide and dexamethasone arm additionally received 16 mg/kg daratumumab once per week (days 1, 8, 15, and 22) during cycles 1 and 2, once every 2 weeks (days 1 and 15) during cycles 3 through 6, and once every 4 weeks going forward. 

Results indicated that OS was significantly higher in the daratumumab plus lenalidomide and dexamethasone arm (67.6 months) than in the lenalidomide and dexamethasone arm alone (51.8 months). Progression-free survival was significantly prolonged in the daratumumab plus lenalidomide and dexamethasone arm (57.9 months) compared to the lenalidomide and dexamethasone arm alone arm (32 months). 

The safety profile of the daratumumab plus lenalidomide and dexamethasone arm was consistent with the results of previous studies, with no new safety hazards detected. The most common grade 3 to 4 treatment-related adverse events in this arm were neutropenia, anemia, pneumonia, thrombocytopenia, and diarrhea. Serious treatment-related adverse events occurred in both arms, pneumonia being the most common. 12.4% (n=35) of patients in the daratumumab plus lenalidomide and dexamethasone arm died due to these events, compared to 8.5% (n=24) in the lenalidomide and dexamethasone alone arm. 

As primary and secondary endpoints were successfully studied, Dr Dimopoulos et al concluded, “[Daratumumab plus lenalidomide and dexamethasone] significantly extended OS versus [lenalidomide and dexamethasone] alone,” adding that these results in addition to previous studies “show an OS benefit with daratumumab-containing regimens in patients with [R/R MM] for the first time.”

Source: 

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:https://doi.org/10.1200/jco.22.00940