Arnaud Pigneux1, Marie C Béné1, Louis-Rachid Salmi1, Pierre-Yves Dumas1, Jacques Delaunay1, Caroline Bonmati1, Romain Guièze1, Isabelle Luquet1, Pascale Cornillet-Lefebvre1, Eric Delabesse1, Jean-Christophe Ianotto1, Mario Ojeda-Uribe1, Mathilde Hunault1, Anne Banos1, Luc Matthieu Fornecker1, Marc Bernard1, Eric Jourdan1, Norbert Vey1, Hacene Zerazhi1, Yosr Hishri1, Ariane Mineur1, Julien Asselineau1, Roselyne Delepine1, Jean-Yves Cahn1, Norbert Ifrah1, Christian Récher1. 1. Arnaud Pigneux and Pierre-Yves Dumas, Bordeaux University Hospital, Bordeaux University, INSERM 1035; Louis-Rachid Salmi, Ariane Mineur, and Julien Asselineau, Bordeaux University Hospital, Bordeaux; Marie C. Béné, and Jacques Delaunay, Nantes University Hospital, Nantes; Caroline Bonmati, Nancy University Hospital, Nancy; Romain Guièze, Clermont-Ferrand University Hospital, Clermont Ferrand; Isabelle Luquet, Eric Delabesse, and Christian Récher, Toulouse University Hospital, Toulouse; Pascale Cornillet-Lefebvre, Reims University Hospital, Reims; Jean-Christophe Ianotto, Brest University Hospital, Brest; Mario Ojeda-Uribe, Mulhouse Regional Hospital, Mulhouse; Mathilde Hunault and Norbert Ifrah, Angers University Hospital and INSERM U 892/CNRS 6299, Angers; Anne Banos, Cote Basque General Hospital, Bayonne; Luc Matthieu Fornecker, Strasbourg University Hospital, Strasbourg; Marc Bernard, Rennes University Hospital, Rennes; Eric Jourdan, Nîmes University Hospital, Nîmes; Norbert Vey, Institut Paoli Calmettes, Marseilles; Hacene Zerazhi, Avignon General Hospital, Avignon; Yosr Hishri, Montpellier University Hospital, Montpellier; Roselyne Delepine, Tours University Hospital, Tours; and Jean-Yves Cahn, Grenoble University Hospital, Grenoble, France.
Abstract
PURPOSE:Acute myeloid leukemia (AML) in elderly patients has a poor prognosis. In an attempt to improve outcome for these patients, the prospective open-label phase III LAM-SA 2007 (Adding Lomustine to Chemotherapy in Older Patients With Acute Myelogenous Leukemia (AML), and Allogeneic Transplantation for Patients From 60 to 65 Years Old) trial randomly assigned patients to astandard induction regimen with lomustine added or to a consolidation regimen with cytarabine and idarubicin. PATIENTS AND METHODS: Adults age 60 years or older with previously untreated AML who were fit to receive intensive chemotherapy and who were without unfavorable cytogenetics receivedstandard chemotherapy with lomustine (idarubicin, cytarabine, and lomustine [ICL]) or without (idarubicin and cytarabine [IC]). The primary objective of the study was overall survival (OS); secondary objectives were response rate, cumulative incidence of relapse (CIR), event-free survival (EFS), and safety. RESULTS:From February 2008 to December 2011, 459 patients were enrolled. Comparing patients in the IC and ICL arms, complete response or complete response with incomplete recovery was achieved in 74.9% versus 84.7% (P = .01). The proportional hazards assumption was rejected for OS (P = .02), which led us to consider two separate time intervals: during and after induction. There was no significant difference between the two arms during induction, although induction deaths were 3.7% versus 7.7%, respectively (P = .11). However, significantly better results were observed after induction with an improved 2-year OS of 56% in the ICL arm versus 48% in the IC arm (P = .02). At 2 years, EFS was improved at 41% in the ICL arm versus 26% in the IC arm (P = .01). The CIR at 2 years was 41.2% in the ICL arm versus 60.9% in the IC arm (P = .003). Grade 3 and 4 toxicities, mostly hematologic, were significantly higher in the ICL arm (P = .04), and fewer patients required a second treatment after ICL. CONCLUSION: Adding lomustine to standard chemotherapy significantly improved the outcome of elderly patients with AML.
RCT Entities:
PURPOSE:Acute myeloid leukemia (AML) in elderly patients has a poor prognosis. In an attempt to improve outcome for these patients, the prospective open-label phase III LAM-SA 2007 (Adding Lomustine to Chemotherapy in Older Patients With Acute Myelogenous Leukemia (AML), and Allogeneic Transplantation for Patients From 60 to 65 Years Old) trial randomly assigned patients to a standard induction regimen with lomustine added or to a consolidation regimen with cytarabine and idarubicin. PATIENTS AND METHODS: Adults age 60 years or older with previously untreated AML who were fit to receive intensive chemotherapy and who were without unfavorable cytogenetics received standard chemotherapy with lomustine (idarubicin, cytarabine, and lomustine [ICL]) or without (idarubicin and cytarabine [IC]). The primary objective of the study was overall survival (OS); secondary objectives were response rate, cumulative incidence of relapse (CIR), event-free survival (EFS), and safety. RESULTS: From February 2008 to December 2011, 459 patients were enrolled. Comparing patients in the IC and ICL arms, complete response or complete response with incomplete recovery was achieved in 74.9% versus 84.7% (P = .01). The proportional hazards assumption was rejected for OS (P = .02), which led us to consider two separate time intervals: during and after induction. There was no significant difference between the two arms during induction, although induction deaths were 3.7% versus 7.7%, respectively (P = .11). However, significantly better results were observed after induction with an improved 2-year OS of 56% in the ICL arm versus 48% in the IC arm (P = .02). At 2 years, EFS was improved at 41% in the ICL arm versus 26% in the IC arm (P = .01). The CIR at 2 years was 41.2% in the ICL arm versus 60.9% in the IC arm (P = .003). Grade 3 and 4 toxicities, mostly hematologic, were significantly higher in the ICL arm (P = .04), and fewer patients required a second treatment after ICL. CONCLUSION: Adding lomustine to standard chemotherapy significantly improved the outcome of elderly patients with AML.
Authors: Sarah Bertoli; Suzanne Tavitian; Pierre Bories; Isabelle Luquet; Eric Delabesse; Thibault Comont; Audrey Sarry; Françoise Huguet; Emilie Bérard; Christian Récher Journal: Cancer Med Date: 2019-06-07 Impact factor: 4.452