PURPOSE: Continuous therapy (CT) prolongs progression-free survival 1 (PFS1; time from random assignment until the first progression or death), but chemotherapy-resistant relapse may negatively impact overall survival (OS). Progression-free survival 2 (PFS2; time from random assignment until the second progression or death) may represent an additional tool to estimate outcome. This study evaluates the benefit of novel agent-based CT versus fixed duration of therapy (FDT) in patients with newly diagnosed myeloma. METHODS: We included patients enrolled onto three phase III trials that randomly assigned patients to novel agent-based CT versus FDT. Primary analyses were restricted to the intent-to-treat population eligible for CT (patients progression free and alive at 1 year after random assignment). Primary end points were PFS1, PFS2, and OS. All hazard ratios (HRs) and 95% CIs were adjusted for several potential confounders using Cox models. RESULTS: In the pooled analysis of the three trials, 604 patients were randomly assigned to CT and 614 were assigned to FDT. Median follow-up was 52 months. In the intent-to-treat CT population, CT (n = 417), compared with FDT (n = 410), significantly improved PFS1 (median, 32 v 16 months, respectively; HR, 0.47; 95% CI, 0.40 to 0.56; P < .001), PFS2 (median, 55 v 40 months, respectively; HR, 0.61; 95% CI, 0.50 to 0.75; P < .001), and OS (4-year OS, 69% v 60%, respectively; HR, 0.69; 95% CI, 0.54 to 0.88; P = .003). CONCLUSION: In this pooled analysis, CT significantly improved PFS1, PFS2, and OS. The improvement in PFS2 suggests that the benefit reported during first remission is not cancelled by a shorter second remission. PFS2 is a valuable end point to estimate long-term clinical benefit and should be included in future trials.

Antonio Palumbo Francesca Gay Federica Cavallo Alessandra Larocca Francesca Donato Chiara Cerrato Luana Boccadifuoco and Mario Boccadoro University of Torino Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino; Giulia Benevolo S C Ematologia A O Città della Salute e della Scienza di Torino; Tommasina Guglielmelli University of Turin and San Luigi Hospital; Giovannino Ciccone Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino and CPO Piemonte Torino; Francesco Di Raimondo Ospedale Ferrarotto Azienda Policlinico OVE University of Catania Catania; Maria T Petrucci Sapienza University of Rome; Tommaso Caravita Ematologia Ospedale S Eugenio Rome; Sara Pezzatti Azienda Ospedaliera San Gerardo Monza; Francesca Patriarca DISM University Hospital Udine; Chiara Nozzoli AOU Careggi Florence; Donatella Vincelli A O Bianchi Melacrino Morelli Reggio Calabria; Pellegrino Musto Istituto di Ricovero e Cura a Carattere Scientifico Referral Cancer Center of Basilicata Rionero in Vulture; Paolo Corradini Fondazione IRCCS Istituto Nazionale dei Tumori University of Milano Milano; Michele Cavo Institute of Hematology and Medical Oncology Seràgnoli Bologna University School of Medicine S Orsola's University Hospital Bologna Italy; Izhar Hardan Meir Medical Center Kfar Saba; Arnon Nagler Tel Aviv University Chaim Sheba Medical Center Tel Hashomer Israel; Roman Hajek University Hospital Ostrava and University of Ostrava Ostrava Czech Republic; Michel Delforge University Hospital Leuven Leuven Belgium; Zhinuan Yu and Christian Jacques Celgene Summit NJ; and Meletios A Dimopoulos National and Kapodistrian University of Athens School of Medicine Alexandra Hospital Athens Greece

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