Benefit of continuous treatment for responders with newly diagnosed multiple myeloma in the randomized FIRST trial

• Published in: Leukemia 2017-11, Vol.31 (11), p.2435-2442
• Main Authors: Bahlis, N J, Corso, A, Mugge, L-O, Shen, Z-X, Desjardins, P, Stoppa, A-M, Decaux, O, de Revel, T, Granell, M, Marit, G, Nahi, H, Demuynck, H, Huang, S-Y, Basu, S, Guthrie, T H, Ervin-Haynes, A, Marek, J, Chen, G, Facon, T
• Format: Article
• Language: English
• Subjects: 631/67/1990/804; 692/700/565/1436/99; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer Research; Comparative analysis; Complications and side effects; Critical Care Medicine; Dexamethasone; Dexamethasone - administration & dosage; Dosage and administration; Drug therapy; Female; Health risk assessment; Hematology; Humans; Intensive; Internal Medicine; Male; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Melphalan; Melphalan - administration & dosage; Middle Aged; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - pathology; Oncology; Original; original-article; Patients; Prednisone; Prednisone - administration & dosage; Randomization; Subgroups; Survival; Thalidomide; Thalidomide - administration & dosage; Thalidomide - analogs & derivatives
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/leu.2017.111

The phase 3, randomized Frontline Investigation of Revlimid and Dexamethasone Versus Standard Thalidomide (FIRST) trial investigating lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) vs melphalan, prednisone and thalidomide for 12 cycles (MPT) and Rd for 18 cycles (Rd18) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) showed that Rd continuous prolonged progression-free survival and overall survival compared with MPT. A subanalysis of the FIRST trial was conducted to determine the benefits of Rd continuous in patients with NDMM based on depth of response. Patients randomized 1:1:1 to Rd continuous, Rd18 or MPT were divided into subgroups based on best response: complete response (CR; n =290), ⩾very good partial response (VGPR; n =679), ⩾partial response (PR; n =1 225) or ⩽stable disease ( n =299). Over 13% of patients receiving Rd continuous who achieved ⩾VGPR as best response did so beyond 18 months of treatment. Rd continuous reduced the risk of progression or death by 67%, 51% and 35% vs MPT in patients with CR, ⩾VGPR and ⩾PR, respectively. Similarly, Rd continuous reduced the risk of progression or death by 61%, 54% and 38% vs Rd18 in patients with CR, ⩾VGPR and ⩾PR, respectively. In patients with CR, ⩾VGPR or ⩾PR, 4-year survival rates in the Rd continuous arm (81.1%, 73.1% or 64.6%, respectively) were higher vs MPT (70.8%, 59.8% or 57.2%, respectively) and similar vs Rd18 (76.5%, 67.7% and 62.5%, respectively). Rd continuous improved efficacy outcomes in all responding patients, including those with CR, compared with fixed duration treatment.