After more than 4 years of follow-up, the addition of daratumumab to lenalidomide and dexamethasone (D-Rd) continues to demonstrate a significant progression-free survival (PFS) benefit and higher rates of deep responses versus lenalidomide and dexamethasone (Rd) alone in patients with relapsed or refractory (R/R) multiple myeloma (MM), according to updated efficacy and safety analyses from the phase 3 POLLUX study. Daratumumab, a human immunoglobulin G κ light chain monoclonal antibody targeting CD38, is approved in combination with standard-of-care regimens for the treatment of newly diagnosed and R/R MM.
In the previously reported POLLUX study (median follow-up, 44.3 months), D-Rd reduced the risk for disease progression or death by 56% and significantly increased the overall response rate (ORR) versus Rd (93% vs 76%; P <.0001) in patients with R/R MM.
A total of 569 patients who had received ≥1 prior lines of therapy were randomized to either D-Rd (N = 286) or to Rd alone (N = 283). Lenalidomide 25 mg was administered orally on days 1 through 21 of each 28-day cycle, dexamethasone was given orally at 40 mg per week, and daratumumab was administered intravenously at 16 mg/kg weekly for cycles 1 to 2, biweekly for cycles 3 through 6, and then every 4 weeks until disease progression. PFS on subsequent line of therapy (PFS2) was an exploratory end point of the study, and was defined as time from randomization to progression after next line of subsequent therapy or death.
At a median follow-up of 54.8 months, D-Rd significantly prolonged PFS versus Rd in the intent-to-treat population, at a median of 45.0 months versus 17.5 months (P <.0001). A PFS benefit with D-Rd was observed among patients who received 1 prior line of therapy (median, 53.3 months vs 19.6 months) and among those refractory to bortezomib (median, 34.3 months vs 11.3 months). D-Rd also improved the rate of minimal residual disease (MRD) negativity and was associated with sustained MRD negativity.
Although a significant PFS benefit was observed with D-Rd in patients regardless of prior lines of therapy or cytogenetic risk status, the greatest benefit was observed when the combination was used in patients treated earlier with the drug triplet, the investigators reported.
Median time to next therapy for patients who received D-Rd was not reached, versus 22.8 months in the Rd group. D-Rd significantly prolonged PFS2 versus Rd (median, 53.3 months vs 31.6 months; P <.0001).
D-Rd was also associated with a significantly higher ORR versus Rd (93% vs 80%), including higher rates of very good partial response or better (80% vs 56%) and complete response or better (59% vs 29%).
The median duration of treatment was 34.3 months in the D-Rd arm versus 16 months in the Rd arm, and no new safety concerns were identified with additional follow-up. The most common (≥10%) grade 3/4 treatment-related adverse events (TRAEs) observed with D-Rd versus Rd included neutropenia (57% vs 42%), anemia (19% vs 22%), thrombocytopenia (15% vs 16%), pneumonia (16% vs 10%), and diarrhea (10% vs 4%). Similar rates of discontinuation due to TRAEs were observed for D-Rd versus Rd (17% vs 15%).
At the time of this analysis, 125 deaths were observed in the D-Rd group versus 144 deaths in the Rd group.
“The significant improvement in PFS2 suggests a potential survival benefit,” noted presenting author Jonathan L. Kaufman, MD, from Emory University, Atlanta, GA. “But overall survival data is still immature.”
According to the investigators, these updated results continue to support the use of daratumumab combination therapies in patients with R/R MM who have received ≥1 prior lines of therapy.
Kaufman JL, et al. ASH Abstract 1866. Session 653.
To sign up for our newsletter or print publications, please enter your contact information below.
