Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study

• Published in: Leukemia Vol. 34; no. 7; pp. 1875 - 1884
• Main Authors: Bahlis, Nizar J., Dimopoulos, Meletios A., White, Darrell J., Benboubker, Lotfi, Cook, Gordon, Leiba, Merav, Ho, P. Joy, Kim, Kihyun, Takezako, Naoki, Moreau, Philippe, Kaufman, Jonathan L., Krevvata, Maria, Chiu, Christopher, Qin, Xiang, Okonkwo, Linda, Trivedi, Sonali, Ukropec, Jon, Qi, Ming, San-Miguel, Jesus
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2020; Nature Publishing Group
• Subjects: 631/67; 692/308; Aged; Antibodies, Monoclonal - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; B cells; Cancer Research; Critical Care Medicine; Development and progression; Dexamethasone; Dexamethasone - administration & dosage; Drug Resistance, Neoplasm - drug effects; Female; Follow-Up Studies; Health risks; Hematology; Humans; Immunotherapy; Intensive; Internal Medicine; Lenalidomide - administration & dosage; Male; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Minimal residual disease; Monoclonal antibodies; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - pathology; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Next-generation sequencing; Oncology; Pharmaceutical industry; Prognosis; Risk assessment; Safety; Salvage Therapy; Schedules; Steroids; Subgroups; Survival Rate; Targeted cancer therapy; Thalidomide - administration & dosage; United States
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/s41375-020-0711-6

In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients ( N  = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1–21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35–0.55; P  < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P  < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P  < 0.0001) and MRD negativity (10 –5 ; 30.4 vs 5.3%; P  < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31–0.50; P  < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42–0.68; P  < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse.