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

Introduction: 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. Methods: 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. Results: 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 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 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 Data for all subgroup analyses will be updated for the meeting. Conclusions: 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. Disclosures Usmani:Britsol-Myers Squibb: Consultancy, Research Funding; Skyline: Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Array: Research Funding; Janssen: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pharmacyclics: Research Funding; BioPharma: Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau; Sanofi: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Dimopoulos:Novartis: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Genesis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees. Belch:Celgene: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria. White:Janssen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees; Celgene: Consultancy, Honoraria. Benboubker:Celgene: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity9s Board of Directors or advisory committees. Cook:Takeda Oncology: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Glycomimetics: Consultancy. Ho:Amgen: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity9s Board of Directors or advisory committees. Khokhar:Janssen: Employment. Guckert:Janssen: Employment; Johnson & Johnson: Equity Ownership. Wu:Janssen: Employment. Qin:Janssen: Employment. Casneuf:Johnson & Johnson: Equity Ownership; Janssen RD Johnson & Johnson: Equity Ownership. San-Miguel:Amgen: Membership on an entity9s Board of Directors or advisory committees; MSD: Membership on an entity9s Board of Directors or advisory committees; Novartis: Membership on an entity9s Board of Directors or advisory committees; Celgene: Membership on an entity9s Board of Directors or advisory committees; Onyx: Membership on an entity9s Board of Directors or advisory committees; Millennium: Membership on an entity9s Board of Directors or advisory committees; BMS: Membership on an entity9s Board of Directors or advisory committees; Janssen: Membership on an entity9s Board of Directors or advisory committees.