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Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML

2019; Elsevier BV; Volume: 3; Issue: 7 Linguagem: Inglês

10.1182/bloodadvances.2018026625

2473-9537

Renato Bassan, Tamara Intermesoli, Arianna Masciulli, Chiara Pavoni, Cristina Boschini, Giacomo Gianfaldoni, Filippo Marmont, Irene Cavattoni, Daniele Mattei, Elisabetta Terruzzi, Lorella De Paoli, Chiara Cattaneo, Erika Borlenghi, Fabio Ciceri, Massimo Bernardi, Anna Maria Scattolin, Elisabetta Todisco, Leonardo Campiotti, Paolo Corradini, Agostino Cortelezzi, Dario Ferrero, Pamela Zanghì, Elena Oldani, Orietta Spinelli, Ernesta Audisio, Sergio Cortelazzo, Alberto Bosi, Brunangelo Falini, Enrico Maria Pogliani, Alessandro Rambaldi,

Hematopoietic Stem Cell Transplantation

Abstract Here we evaluated whether sequential high-dose chemotherapy (sHD) increased the early complete remission (CR) rate in acute myelogenous leukemia (AML) compared with standard-intensity idarubicin-cytarabine-etoposide (ICE) chemotherapy. This study enrolled 574 patients (age, 16-73 years; median, 52 years) who were randomly assigned to ICE (n = 286 evaluable) or sHD (2 weekly 3-day blocks with cytarabine 2 g/m2 twice a day for 2 days plus idarubicin; n = 286 evaluable). Responsive patients were risk-stratified for a second randomization. Standard-risk patients received autograft or repetitive blood stem cell-supported high-dose courses. High-risk patients (and standard-risk patients not mobilizing stem cells) underwent allotransplantation. CR rates after 2 induction courses were comparable between ICE (80.8%) and sHD (83.6%; P = .38). sHD yielded a higher single-induction CR rate (69.2% vs 81.5%; P = .0007) with lower resistance risk (P < .0001), comparable mortality (P = .39), and improved 5-year overall survival (39% vs 49%; P = .045) and relapse-free survival (36% vs 48%; P = .028), despite greater hematotoxicity delaying or reducing consolidation blocks. sHD improved the early CR rate in high-risk AML (odds ratio, 0.48; 95% confidence interval [CI], 0.31-0.74; P = .0008) and in patients aged 60 years and less with de novo AML (odds ratio, 0.46; 95% CI, 0.27-0.78; P = .003), and also improved overall/relapse-free survival in the latter group (hazard ratio, 0.70; 95% CI, 0.52-0.94; P = .01), in standard-risk AML, and postallograft (hazard ratio, 0.61; 95% CI, 0.39-0.96; P = .03). sHD was feasible, effectively achieved rapid CR, and improved outcomes in AML subsets. This study is registered at www.clinicaltrials.gov as #NCT00495287.