Treatment Intensification With Either Fludarabine, AraC, G-CSF and Idarubicin, or Cladribine Plus Daunorubicin and AraC on the Basis of Residual Disease Status in Older Patients With AML: Results From the NCRI AML18 Trial.

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 DA: hazard ratio [HR], 0.74 [95% CI, 0.55 to 1.01]; = .054; FLAG-Ida DA: HR, 0.86 [95% CI, 0.66 to 1.12]; = .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 4% after DA or DAC; = .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]; = .018) and FLAG-Ida (HR, 0.72 [95% CI, 0.53 to 0.98]; = .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 DA: HR, 0.66 [95% CI, 0.45 to 0.98]; = .039; FLAG-Ida DA: HR, 0.70 [95% CI, 0.49 to 0.99]; = .042). DAC benefit was maintained when survival was censored for transplant ( = .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.

ErratumIn

J Clin Oncol. 2025 Jan 10;43(2):239. doi: 10.1200/JCO-24-02577.

COI Statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

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