No Survival Benefit to Fourth Chemo Course in Younger Patients with AML

No Survival Benefit to Fourth Chemo Course in Younger Patients with AML
No Survival Benefit to Fourth Chemo Course in Younger Patients with AML

ORLANDO, FLIn younger patients with good and standard risk acute myeloid leukemia (AML), there is no survival benefit to a fourth course of chemotherapy, although risk of relapse was significantly reduced without increasing deaths in remission, Nigel H. Russell, MD, of the Centre for Clinical Haematology at Nottingham University Hospital in the United Kingdom, told colleagues attending the 57th American Society of Hematology (ASH) Annual Meeting.

Speaking on behalf of the UK National Cancer Research Institute AML Working Party, Dr. Russell summarized the first results from the AML17 trial in 1,107 patients up to 60 years of age with AML or high-risk myelodysplastic syndrome (MDS) who were allocated to study treatment based on risk.

Previous work has shown that “while patients with poor-risk disease had better outcomes with 4 courses, any effect of a fourth course was much less clear for patients with good or standard risk disease,” he said in explaining the rationale for their study.

Following their first course of treatment, study patients were allocated to a risk group based on a validated score that comprised cytogenetics, white blood cell count, age, secondary disease, and blast response to the first course.

“Patients who failed to achieve at least a 50% reduction in blasts were considered poor risk,” he said. Also included in the poor-risk group were those at otherwise standard risk but FLT-3 ITD mutant/NPM1c wild type.

From July 2009 to June 2015, adults in the good or standard risk group were randomly assigned after 2 courses of treatment (DA or ADE, with or without gemtuzumab ozogamicin 3/6 mg/m2) to receive 1 or 2 courses of consolidation (3 or 4 courses in total). Median age was 48 years (range, 16-72 years); 45% were male; and 4% had WHO PS of 2 or higher. A total of 24% had core binding factor (CBF) leukemia; 76% had intermediate-risk disease; 1% had secondary disease; and 3% had MDS.

Prior to mid-2010, patients were randomly assigned to recieve MACE/MidAC or MACE; however, based on AML15 study results, consolidation was amended to 1 or 2 courses of Ara-C 3 g/m2/d for 5 days.

As of March 1, 2015, median follow-up for survival was 28.8 months (range, 0.1-68.2 months).

At 5 years, the overall survival rate was 57%, Dr. Russell said, which did not differ significantly between the arms (58% vs 55%; HR 0.90 [0.71-1.14]; P = .4), which reflected the effect of salvage: 3 year survival from relapse was 32% vs 31% (HR 0.97 [0.75-1.26]; P = .8).

“An additional course of consolidation reduced relapse (CIR 53% vs 57%; HR 0.81 [0.67-0.99]; P = .04), with no difference in death in remission (7% vs 6%; HR 1.10 [0.61-2.00]; P = 0.8), leading to some evidence of improved relapse-free survival (41% vs 37%, HR 0.84 [0.70-1.01]; P = .06),” he noted.

Stratified analyses showed that “4 courses may result in better survival for subgroups including FLT3-ITD wild type patients and those with lower WBC” counts at diagnosis, he said.

The extra course showed no survival difference by cytogenetics, although relapse was reduced more for patients with CBF leukemias. For patients for whom data on minimal residual disease were available, “there was no evidence of a differential effect of an extra course of consolidation by MRD status” after either the first or second course.

“Attention now turns to whether the use of more intensive induction regimens such as FLAG-Ida can improve outcomes while delivering fewer courses,” Dr. Russell concluded.

Reference

1. Russell NH, Hills RK, Freeman S, et al. A comparison of 1 or 2 courses of high dose cytarabine as consolidation in younger patients with AML: first results of the UK NCRI AML17 Trial. Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting; December 6, 2015, Orlando, FL.

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