Daratumumab is an anti-CD38 IgGκ monoclonal antibody that has been successfully combined with lenalidomide/dexamethasone for the treatment of multiple myeloma (MM). The randomized phase 3 POLLUX trial found this triplet (DRd) to be markedly superior to lenalidomide/dexamethasone (Rd) alone in relapsed/refractory MM patients.
Investigators led by Moreau performed subgroup analyses to further examine the efficacy of the triplet according to prior treatment exposure. Patients who received ≥1 prior lines of therapy (but were not refractory to lenalidomide) were randomized to Rd, with or without daratumumab (DRd) until progression. The primary end point was progression-free survival (PFS).
The analysis showed significant benefit for the daratumumab arm in the following subsets:
- Lenalidomide-naïve (n = 445): Median PFS was not reached with DRd versus 17.1 months with Rd. The estimated 12-month PFS rates were 77% compared with 50%, respectively.
- Lenalidomide-exposed (n = 91): Median PFS was not reached in both treatment groups. The estimated 12-month PFS rates were 79% versus 59%, respectively.
- Bortezomib-refractory (n = 103): Median PFS was not reached with DRd versus 10.3 months with Rd. The estimated 12-month PFS rates were 65% versus 40%, respectively.
With regard to minimal residual disease (MRD) status, 25% of patients in the evaluable population receiving DRd achieved MRD-negative status at 10-5 compared with 6% of patients receiving Rd.
The authors concluded that in patients who previously received lenalidomide or bortezomib, the addition of daratumumab produced more responses and deeper responses. These results strengthen the significant benefit shown for DRd in relapsed/refractory MM.
Moreau P, et al. ASH 2016. Abstract 489.