AML

Defining the Optimal Total Number of Chemotherapy Courses in Younger Patients with Acute Myeloid Leukemia: A Comparison of Three Versus Four Courses

Defining the Optimal Total Number of Chemotherapy Courses in Younger Patients with Acute Myeloid Leukemia: A Comparison of Three Versus Four Courses

In the January 7, 2021 edition of Journal of Clinical Oncology,  investigators report on the optimal number of chemotherapy courses in AML patients

PURPOSE

The United Kingdom National Cancer Research Institute AML17 trial randomly assigned newly diagnosed non-high risk AML patients to either 3 or 4 cycles of chemotherapy, to determine the benefit of an additional cycle of chemotherapy

PATIENTS AND METHODS

Patients had been treated with two induction courses utilizing daunorubicin and cytarabine (Ara-C), the majority of them coupled with gemtuzumab ozogamicin. Following remission, 1,017 patients were randomized to a third course, MACE (amsacrine, Ara-C, and etoposide), plus a fourth course of MidAc (mitoxantrone and Ara-C) and 1-2 courses of high-dose Ara-C.  The primary end points were cumulative incidence of relapse (CIR), OS, and RFS.

RESULTS

Utilizing logrank analyses, CIR and RFS at 16 months were improved in patients who underwent for courses (50% versus 58%: HR 0.81 [0.69-0.97], P = .02 and 43% versus 36%: HR 0.83 [0.71-0.98], P = .03, respectively). While the overall survival was not significantly better (63% versus 57%: HR 0.84 [0.69-1.03], P = .09), the noninferiority of 3 versus 4 courses was not established per the investigators. The impact on relapse was only significant when the fourth course was Ara-C.  After performing exploratory analysis, a fourth course showed no effect in either MRD-positive or MRD-negative patients. A fourth course was shown to be beneficial in patients who had no evidence of a FLT3 or NPM1 mutation, also with < 3 mutations in other genes, or had a presenting WBC of < 10K.

The authors concluded “Although a fourth course of high-dose Ara-C reduced CIR and improved RFS, it did not result in a significant OS benefit. Subsets including those with favorable cytogenetics, those lacking a mutation of FLT3 or NPM1, or those with < 3 other mutations may derive survival benefit.”

https://ascopubs.org/doi/full/10.1200/JCO.20.01170

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