Three-Year Follow up of the Phase 3 Pollux Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) Alone in Relapsed or Refractory Multiple Myeloma (RRMM)

Abstract

Introduction: Daratumumab is a human, CD38-targeted, IgGκ monoclonal antibody with both direct on-tumor and immunomodulatory mechanisms of action. In the phase 3 POLLUX study, D-Rd reduced the risk of disease progression or death by 63% and significantly increased the overall response rate (ORR) versus Rd alone (93% vs 76%; P 3 years of median follow-up. Methods: Pts with ≥1 prior line of therapy were randomized (1:1) to receive Rd (lenalidomide 25 mg PO on Days 1-21 of each 28-day cycle; dexamethasone 40 mg per week) ± daratumumab (16 mg/kg IV QW for Cycles 1-2, Q2W for Cycles 3-6, then Q4W until disease progression). High risk cytogenetic abnormalities included t(4;14), t(14;16), and del17p. At the time of suspected CR and at 3 and 6 months after confirmed CR (and every 12 months thereafter if CR was maintained), bone marrow aspirates were assessed for MRD using clonoSEQ® V2.0 (Adaptive Biotechnologies, Seattle, WA). Sustained MRD negativity was defined as maintenance of MRD negativity at the 10-5 threshold for ≥6 or ≥12 months. PFS on subsequent line of therapy (PFS2), an exploratory endpoint, was defined as time from randomization to progression after next line of subsequent therapy or death. Results: A total of 569 pts were randomized (D-Rd, n = 286; Rd, n = 283). At a median follow-up of 39.5 months, D-Rd significantly prolonged progression-free survival (PFS) versus Rd (median, not reached [NR] vs 17.5 months; hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.35-0.55; P The median duration of treatment was 34.3 months in the D-Rd arm versus 16.0 months in the Rd arm. The most common (≥10%) grade 3/4 treatment-emergent adverse events (TEAEs) observed with D-Rd versus Rd are described in Table 2. No differences were observed for D-Rd versus Rd in discontinuations due to TEAEs (14% of pts in each treatment group) or incidences of second primary malignancies (7% of pts in each treatment group). Updated data including PFS2 will be presented at the meeting. Conclusion: After >3 years of median follow-up, D-Rd continued to demonstrate a significant PFS benefit and higher rates of deeper responses versus Rd alone in RRMM pts. The higher rate of sustained MRD negativity with D-Rd compared with Rd suggests that continued D-Rd treatment drives these deep responses and delays progression. No new safety signals were observed following a median of 34 months of D-Rd exposure. Disclosures Bahlis:Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Dimopoulos:Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria. White:Amgen: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity9s Board of Directors or advisory committees. Cook:Amgen, Bristol-Myers Squibb, GlycoMimetics, Celgene, Janssen and Takeda and Sanofi: Honoraria; Celgene, Janssen and Takeda: Research Funding. Ho:Takeda: Honoraria, Other: Travel to meeting; Novartis: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene: Other: Travel to meeting. Moreau:Janssen: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity9s Board of Directors or advisory committees. Krevvata:Janssen Research & Development, LLC: Employment. Chiu:Janssen Research & Development, LLC: Employment. Qin:Janssen Research & Development, LLC: Employment. Okonkwo:Janssen Research & Development, LLC: Employment. Trivedi:Janssen Research & Development, LLC: Employment. Qi:Janssen Research & Development, LLC: Employment. San-Miguel:Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria; BMS: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; Roche: Honoraria.