Background
Randomized phase 3 trial of 569 patients with relapsed/refractory multiple myeloma who had received ≥1 prior line, comparing daratumumab plus lenalidomide and dexamethasone (Dara-Rd) vs lenalidomide and dexamethasone (Rd). This report presents updated efficacy at extended follow-up.
Interventions and follow up
Arm A (Dara-Rd): Daratumumab 16 mg/kg IV QW x8, then Q2W x16, then Q4W until progression + Rd
Arm B (Rd): Lenalidomide 25 mg PO D1-21 Q28D + dexamethasone 40 mg weekly
Primary endpoint: PFS
Median follow-up: 44 months
Arm B (Rd): Lenalidomide 25 mg PO D1-21 Q28D + dexamethasone 40 mg weekly
Primary endpoint: PFS
Median follow-up: 44 months
Results
Median PFS: 44.5 months (Dara-Rd) vs 17.5 months (Rd); HR 0.44, 95% CI 0.35-0.55, P<.001
MRD negativity rates were higher with Dara-Rd
MRD negativity rates were higher with Dara-Rd
Adverse events
Hematologic: Neutropenia (most common treatment-emergent event) 63.3% (Dara-Rd) vs 48% (Rd)
Other: Pulmonary embolism 0% vs 1%; second primary malignancy 8.5% vs 8.9% (similar)
Other: Pulmonary embolism 0% vs 1%; second primary malignancy 8.5% vs 8.9% (similar)
Conclusions
In relapsed/refractory multiple myeloma, daratumumab added to lenalidomide and dexamethasone resulted in significantly improved PFS compared with Rd alone, with deep and durable responses sustained at extended follow-up.
Key Limitations
Many enrolled patients were lenalidomide-naive, limiting applicability to the now-common lenalidomide-exposed early-relapse population. Higher rates of neutropenia and infusion reactions with daratumumab. OS data were immature at this analysis.
Clinical Context
POLLUX supported FDA and EMA approval of daratumumab plus Rd for relapsed/refractory multiple myeloma after ≥1 prior therapy. Dara-Rd is a preferred regimen for lenalidomide-naive relapse per ASCO and ESMO guidance; CD38-antibody triplets are now standard early-relapse therapy.