Russell, Nigel H., Thomas, Abin ![]() ![]() ![]() |
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Abstract
Purpose: To evaluate the survival benefit of chemotherapy intensification in older patients with AML who have not achieved a measurable residual disease (MRD)–negative remission. Methods: Five hundred twenty-three patients with AML (median age, 67 years; range, 51-79) without a flow cytometric MRD-negative remission response after a first course of daunorubicin and AraC (DA; including 165 not in remission) were randomly assigned between up to two further courses of DA or intensified chemotherapy—either fludarabine, cytarabine, granulocyte colony-stimulating factor and idarubicin (FLAG-Ida) or DA with cladribine (DAC). Results: Overall survival (OS) was not improved in the intensification arms (DAC v DA: hazard ratio [HR], 0.74 [95% CI, 0.55 to 1.01]; P = .054; FLAG-Ida v DA: HR, 0.86 [95% CI, 0.66 to 1.12]; P = .270); OS at 3 years was 34%, 46%, and 42% for DA, DAC, and FLAG-Ida, respectively. Early deaths and other adverse events were more frequent with FLAG-Ida (9% day 60 deaths v 4% after DA or DAC; P = .032). Of patients entering random assignment, 131 had MRD unknown status. In this subgroup of patients lacking evidence of residual leukemia by flow cytometry, there was no detectable survival advantage from intensification. A planned sensitivity analysis excluding these patients demonstrated a survival benefit for both DAC (HR, 0.66 [95% CI, 0.46 to 0.93]; P = .018) and FLAG-Ida (HR, 0.72 [95% CI, 0.53 to 0.98]; P = .035); OS at 3 years was 30%, 46%, and 46% for DA, DAC, and FLAG-Ida, respectively. There was a concordant reduction in relapse (DAC v DA: HR, 0.66 [95% CI, 0.45 to 0.98]; P = .039; FLAG-Ida v DA: HR, 0.70 [95% CI, 0.49 to 0.99]; P = .042). DAC benefit was maintained when survival was censored for transplant (P = .042). Conclusion: In this study of older patients with AML considered fit and with evidence of residual disease after first induction, chemotherapy intensification improved survival. DAC intensification was better tolerated than FLAG-Ida.
Item Type: | Article |
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Date Type: | Published Online |
Status: | In Press |
Schools: | Centre for Trials Research (CNTRR) Medicine |
Publisher: | American Society of Clinical Oncology |
ISSN: | 0732-183X |
Date of First Compliant Deposit: | 9 January 2025 |
Date of Acceptance: | 10 October 2024 |
Last Modified: | 09 Jan 2025 15:11 |
URI: | https://orca.cardiff.ac.uk/id/eprint/175153 |
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