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Scientific article
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English

Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia

Published inBlood, vol. 125, no. 24, p. 3711-3719
Publication date2015-06-11
Abstract

In this study, we randomly compared high doses of the tyrosine kinase inhibitor imatinib combined with reduced-intensity chemotherapy (arm A) to standard imatinib/hyperCVAD (cyclophosphamide/vincristine/doxorubicin/dexamethasone) therapy (arm B) in 268 adults (median age, 47 years) with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). The primary objective was the major molecular response (MMolR) rate after cycle 2, patients being then eligible for allogeneic stem cell transplantation (SCT) if they had a donor, or autologous SCT if in MMolR and no donor. With fewer induction deaths, the complete remission (CR) rate was higher in arm A than in arm B (98% vs 91%; P = .006), whereas the MMolR rate was similar in both arms (66% vs 64%). With a median follow-up of 4.8 years, 5-year event-free survival and overall survival (OS) rates were estimated at 37.1% and 45.6%, respectively, without difference between the arms. Allogeneic transplantation was associated with a significant benefit in relapse-free survival (hazard ratio [HR], 0.69; P = .036) and OS (HR, 0.64; P = .02), with initial white blood cell count being the only factor significantly interacting with this SCT effect. In patients achieving MMolR, outcome was similar after autologous and allogeneic transplantation. This study validates an induction regimen combining reduced-intensity chemotherapy and imatinib in Ph+ ALL adult patients and suggests that SCT in first CR is still a good option for Ph+ ALL adult patients. This trial was registered at www.clinicaltrials.gov as #NCT00327678.

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Keywords
  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / toxicity
  • Benzamides / administration & dosage
  • Benzamides / therapeutic use
  • Benzamides / toxicity
  • Disease-Free Survival
  • Female
  • Humans
  • Imatinib Mesylate
  • Male
  • Middle Aged
  • Philadelphia Chromosome
  • Piperazines / administration & dosage
  • Piperazines / therapeutic use
  • Piperazines / toxicity
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / therapeutic use
  • Protein Kinase Inhibitors / toxicity
  • Pyrimidines / administration & dosage
  • Pyrimidines / therapeutic use
  • Pyrimidines / toxicity
  • Stem Cell Transplantation
  • Treatment Outcome
  • Young Adult
Citation (ISO format)
CHALANDON, Yves et al. Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia. In: Blood, 2015, vol. 125, n° 24, p. 3711–3719. doi: 10.1182/blood-2015-02-627935
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Identifiers
ISSN of the journal0006-4971
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