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J Clin Oncol. 2015 Oct 20;33(30):3459-66. doi: 10.1200/JCO.2014.60.2466. Epub 2015 Aug 17.

Continuous Therapy Versus Fixed Duration of Therapy in Patients With Newly Diagnosed Multiple Myeloma.

Author information

1
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 (IRCCS), 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. appalumbo@yahoo.com.
2
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 (IRCCS), 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.

Abstract

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.

PMID:
26282661
DOI:
10.1200/JCO.2014.60.2466
[Indexed for MEDLINE]

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