Final analysis of survival outcomes in the randomized phase 3 FIRST trial
Mené sur 1 623 patients atteints d'un myélome multiple récemment diagnostiqué et inéligibles pour une greffe, cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un traitement combinant lénalidomide et dexaméthasone en faibles doses dispensé de façon continue, ce même traitement dispensé sur 18 cycles pendant 72 semaines, et un traitement à base de melphalan, prednisone et thalidomide (durée médiane de suivi : 67 mois)
This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ≥ 60 months’ follow-up). Patients were randomized to Rd continuous (n = 535), Rd18 (n = 541), or MPT (n = 547). At a median follow-up of 67 months, PFS was significantly longer with Rd continuous vs MPT (HR, 0.69; 96% CI, 0.59-0.79; P < .00001) and was similarly extended vs Rd18. Median OS was 10 months longer with Rd continuous vs MPT (59.1 vs 49.1 months; HR, 0.78; 95% CI, 0.63-0.95; P = .0144), and similar with Rd18 (62.3 months). In patients achieving complete or very good partial responses, Rd continuous had a ≈ 30-month-longer median time to next treatment vs Rd18 (69.5 vs 39.9 months). Over half of all patients who received second-line treatment were given a bortezomib-based therapy. Second-line outcomes were improved in patients receiving bortezomib after Rd continuous and Rd18 vs after MPT. No new safety concerns, including risk for secondary malignancies, were observed. Treatment with Rd continuous significantly improved survival outcomes vs MPT, supporting Rd continuous as a standard of care for patients with transplant-ineligible NDMM. Study registration is at Clinicaltrials.gov (NCT00689936) and EudraCT (2007-004823-39).
Blood 2017