Administering 2 additional courses of chemotherapy with high-dose cytarabine (Ara-C) after 2 courses of induction therapy improved relapse rates but did not improve overall survival for patients with acute myeloid leukemia (AML), according to research in the Journal of Clinical Oncology.1 

For patients with AML who are younger than age 60 years, the optimal number of chemotherapy courses has been unclear. Previous studies found that 5 total courses offered no additional benefit over 4 courses of treatment.2,3 Therefore, a team of investigators conducted an analysis to determine whether 3 or 4 courses of treatment improved patient outcomes for patients with AML. The primary outcome of the study measured overall survival at 5 years, as well as cumulative incidence of relapse and relapse-free survival (RFS). 

The study included 1017 patients who had received 2 courses of induction therapy, were in remission, were aged 60 years or younger, and were not considered high risk. Participants were randomly assigned to receive the third course (n=510; amsacrine, Ara-C, and etoposide) and fourth courses (n=517; mitoxantrone and Ara-C). Results from the MRC AML15 trial led the researchers to amend the protocol to randomly assign patients to either 1 or 2 additional courses of high-dose Ara-C; 885 patients received Ara-C exclusively per the amended protocol.

Compared with patients who received 3 courses, patients who received 4 courses had a reduced cumulative incidence of relapse (50% vs 58%, respectively; P =.02) and improved RFS (43% vs 36%, respectively; P =.03).


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The overall survival did not significantly differ between 3 and 4 courses (63% vs 56%, respectively), and noninferiority was not established (P ­=.09). Although measurable residual disease (MRD) is often predictive of relapse, a fourth treatment course did not improve overall survival for MRD-positive or MRD-negative patients.

The investigators noted that some patients with favorable cytogenetics may benefit from 2 additional courses with high-dose Ara-C. Patients without an FLT3 or NPM1 mutations, or patients with less than 3 mutations, may have the greatest survival benefit.

Patients who received 4 courses of therapy had more days in hospital, more days on antibiotics, and needed more blood products compared with patients who were treated with 3 courses; however, patients with 3 total courses, had higher rates of relapse, leading to higher rates of salvage transplants.

“Overall, this experience suggests that if Ara-C is the chosen consolidation treatment, a fourth course of overall treatment is probably beneficial,” the authors noted.

Disclosure: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

References

  1. Burnett AK, Russell NH, Hills RK, et al. Defining the optimal total number of chemotherapy courses in younger patients with acute myeloid leukemia: a comparison of three versus four courses. J Clin Oncol. Published online December 23, 2020. doi:10.1200/JCO.20.01170
  2. Burnett AK, Hills RK, Milligan DW, et al. Attempts to optimize induction and consolidation treatment in acute myeloid leukemia: results of the MRC AML12 trial. J Clin Oncol. 2010;28(4):586-595. doi: 10.1200/JCO.2009.22.9088
  3. Burnett AK, Russell NH, Hills RK, et al. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the Medical Research Council AML15 trial. J Clin Oncol. 2013;31(27):3360-3368. doi: 10.1200/JCO.2012.47.4874