Saad Z. Usmani, MD
Levine Cancer Institute
Efficacy of Daratumumab, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma Patients with 1 to 3 Prior Lines of Therapy: Updated Analysis of Pollux
Daratumumab is a human monoclonal antibody targeting CD38 that demonstrated superior efficacy in combination with lenalidomide and dexamethasone (DRd) versus lenalidomide and dexamethasone alone (Rd) in a pre-specified interim analysis of a randomized phase 3 study of relapsed or refractory multiple myeloma (RRMM; Dimopoulos MA, et al. N Engl J Med 2016; in press). We report subgroup analyses from this study in patients (pts) who received 1 to 3 prior lines of therapy (1-3 PL), including outcomes based on high-risk cytogenetics within these subgroups.
Patients (pts) who received ≥1 prior line of therapy were randomized (1:1) to Rd (lenalidomide: 25 mg PO on Days 1-21 of each 28-day cycle; dexamethasone: 40 mg PO weekly) with or without daratumumab (16 mg/kg IV qw for 8 weeks, q2w for 16 weeks, then q4w until progression). The primary endpoint was progression-free survival (PFS). The site investigator determined the number of prior lines of therapy according to IMWG consensus guidelines. Treatment-free interval (TFI) was defined as the duration between the end/start date of last line of prior therapy and the date of randomization. Pts with high-risk cytogenetic status had at least one of the following abnormalities as assessed via fluorescence in-situ hybridization or karyotyping by local laboratory assessment: t(4;14), t(14;16), or del17p.
In the 1-3 PL subgroup (DRd, n=272; Rd, n=264), PFS was significantly improved with DRd vs Rd (median: not reached [NR] vs 18.4 months; HR, 0.36; 95% CI, 0.25-0.50; P<0.0001), with estimated 12-month PFS rates of 83.2% vs 60.4%, respectively. Time to progression was also significantly longer with DRd vs Rd (median: NR vs 18.4 months; HR, 0.32; 95% CI, 0.22-0.46; P<0.0001). ORR (94% vs 77%), rates of very good partial response (VGPR) or better (76% vs 45%) and complete response (CR) or better (44% vs 20%) were significantly higher with DRd vs Rd, respectively (P<0.0001 for all). Among responders, median time to VGPR or better was 2.8 months in DRd vs 2.9 months in Rd; median time to CR or better was 6.7 months vs 7.5 months, respectively. For pts in the 1-3 PL subgroup with high-risk cytogenetics (n=33 in each treatment group), significantly longer PFS was observed in DRd vs Rd (median: NR vs 8.3 months; HR, 0.30; 95% CI, 0.14-0.67; P=0.0019). Significantly higher ORR (91% vs 69%; P=0.0267), rate of VGPR or better (73% vs 28%; P=0.0004), and rate of CR or better (36% vs 9%; P=0.0104) were achieved in pts with high-risk cytogenetic status treated with DRd vs Rd, respectively.
For 1-3 PL pts who had a TFI of >12 months (DRd, n=138; Rd, n=145), median PFS was NR in DRd vs 18.4 months in Rd (HR, 0.42; 95% CI, 0.24-0.74; P=0.0019; Figure A); the estimated 12-month PFS rate was 88.0% vs 74.5%, respectively. ORR was significantly higher with DRd vs Rd (96% vs 86%, P=0.0084), along with rate of VGPR or better (77% vs 56%; P=0.0008) and rate of CR or better (43% vs 27%; P=0.0083). Among pts with a TFI of ≤12 months (DRd, n=134; Rd, n=119), median PFS was NR in DRd vs 10.3 months in Rd (HR, 0.32; 95% CI, 0.21-0.51; P<0.0001; Figure B); the estimated 12-month PFS rate was 78.1% vs 43.1%, respectively. ORR (92% vs 67%), rate of VGPR or better (76% vs 32%), and rate of CR or better (44% vs 10%) were all significantly higher with DRd vs Rd (P<0.0001 for all).
Among pts with 1-3 PL who were refractory to their last line of therapy (DRd, n=73; Rd, n=67), PFS was significantly prolonged with DRd vs Rd (median: NR vs 10.3 mo; HR, 0.42; 95% CI, 0.25-0.72; P=0.0010). ORR (92% vs 66%; P=0.0002), rate of VGPR or better (72% vs 34%; P<0.0001), and rate of CR or better (47% vs 14%; P<0.0001) were significantly higher with DRd vs Rd.
Data for all subgroup analyses will be updated for the meeting.
Responses with DRd were deep and durable which translated into significantly improved clinical outcomes vs Rd in 1-3 PL pts with RRMM. The results of these subgroup analyses suggest that the treatment benefit of DRd vs Rd was maintained across these subgroups, including pts with TFI of ≤12 months and those who were refractory to their last line of therapy.