Pomalidomide/Daratumumab/Dexamethasone in Relapsed or Refractory Multiple Myeloma: Final Overall Survival From MM-014

• Published in: Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2024-12, Vol.24 (12), p.852-862
• Main Authors: Bahlis, Nizar J., Samaras, Christy, Reece, Donna, Sebag, Michael, Matous, Jeffrey, Berdeja, Jesús G., Shustik, Jesse, Schiller, Gary J., Ganguly, Siddhartha, Song, Kevin, Seet, Christopher S., Acosta-Rivera, Mirelis, Bar, Michael, Quick, Donald, Fonseca, Gustavo, Liu, Hongjuan, Gentili, Christian, Singh, Pavit, Siegel, David
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Dexamethasone - administration & dosage; Dexamethasone - therapeutic use; DPd; Drug Resistance, Neoplasm; Efficacy; Female; Humans; Immunomodulatory agent; Lenalidomide-exposed; Male; Middle Aged; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - mortality; Thalidomide - administration & dosage; Thalidomide - analogs & derivatives; Thalidomide - pharmacology; Thalidomide - therapeutic use; Toxicity management; Treatment Outcome
• ISSN: 2152-2650; 2152-2669; 2152-2669
• DOI: 10.1016/j.clml.2024.07.014

•MM-014 cohort B final OS data at a median follow-up of 41.9 months were reported.•DPd resulted in favorable OS in patients with RRMM who had received prior LEN.•IMiD agent-based therapy can still be considered after disease progression on or after LEN.•Safety profile was consistent with previous reports. Patients with relapsed or refractory multiple myeloma (RRMM) who have exhausted lenalidomide benefits require improved therapies. The 3-cohort phase 2 MM-014 trial (NCT01946477) explored pomalidomide in early lines of treatment for lenalidomide-exposed RRMM. In cohort B, pomalidomide plus daratumumab and dexamethasone (DPd) showed promising efficacy (median follow-up 28.4 months), as previously reported. Here, we report final overall survival (OS) in cohort B. Patients aged ≥ 18 years were treated in 28-day cycles: pomalidomide 4 mg orally daily from days 1 to 21; daratumumab 16 mg/kg intravenously on days 1, 8, 15, and 22 (cycles 1-2), days 1 and 15 (cycles 3-6), and day 1 (cycle ≥ 7); and dexamethasone 40 mg (age ≤ 75 years) or 20 mg (age > 75 years) orally on days 1, 8, 15, and 22. The primary endpoint was ORR. OS and safety were secondary endpoints. Among 112 patients enrolled, 85 (75.9%) had lenalidomide-refractory disease and 27 (24.1%) had lenalidomide-relapsed disease. At a median follow-up of 41.9 months (range, 0.4-73.1), median OS was 56.7 months (95% confidence interval, 46.5-not reached). Treatment-emergent adverse events related to, and leading to discontinuation of, pomalidomide, dexamethasone, or daratumumab occurred in 7 (6.3%), 9 (8.0%), and 6 (5.4%) patients, respectively. With long-term follow-up, our results show favorable OS with DPd. The safety profile was consistent with previous reports, with no new safety signals identified. IMiD agent-based therapy can still be considered in patients with RRMM who experience progressive disease on or after lenalidomide. The 3-cohort MM-014 trial explored pomalidomide for lenalidomide-exposed relapsed or refractory multiple myeloma. In cohort B, patients with 1 to 2 prior lines were treated with pomalidomide/daratumumab/dexamethasone. Median overall survival was 56.7 months (95% confidence interval, 46.5-not reached; median follow-up, 41.9); no new safety signals were identified. IMiD agent-based therapy can still be considered following progressive disease on or after lenalidomide.