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Rebecca Olin, MD, MS

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What Is the Optimal Number of Chemotherapy Courses for Younger Patients With AML?

By: Cordi Craig, MS
Posted: Tuesday, March 23, 2021

The optimal number of chemotherapy courses for younger patients with acute myeloid leukemia (AML) remains unclear. According to the United Kingdom National Cancer Research Institute AML17 trial, some younger patients with AML may derive greater benefit from four courses versus three courses of chemotherapy. Alan K. Burnett, MD, of Cardiff University School of Medicine, United Kingdom, and colleagues reported that although a fourth course of high-dose cytarabine, the standard of care for AML, appeared to reduce the cumulative incidence of relapse and improve relapse-free survival, no overall survival benefit was observed. The results were published in the Journal of Clinical Oncology.

Eligible patients included those who had achieved remission following two induction courses based on daunorubicin and cytarabine, usually with gemtuzumab ozogamicin. The researchers randomly assigned 1,017 patients to receive a third course of amsacrine, etoposide, and cytarabine, plus a fourth course of mitoxantrone and cytarabine. A subsequent protocol amendment changed the fourth course to one or two courses of high-dose cytarabine.

The cumulative incidence of relapse was 50%, and it was 58% among those who were treated with four courses versus three courses of chemotherapy (P = .02). The relapse-free survival rate was significantly higher among patients who received four courses versus three courses of chemotherapy (43% vs. 36%; P = .03). However, the beneficial impact on relapse was significant only when the fourth course of chemotherapy was cytarabine. No significant difference in overall survival was observed between the two groups (P = .09). Three courses of chemotherapy appeared to be noninferior to four courses.

Exploratory analyses indicated that although measurable residual disease (MRD) impacted survival, a fourth course seemed to have no effect in either patients with MRD-positive or MRD-negative disease. Specific patient subgroups may derive survival benefits, such as those with favorable cytogenetics, those lacking a mutation of FLT3 and NPM1, or those with fewer than three other mutations.

Disclosure: For full disclosures of the study authors, visit ascopubs.org.


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