Retrospective Analysis of Survival in Patients with Acute Erythroid Leukemia (AML-6) Treated with Conventional Chemotherapy Versus Hypomethylating Agents
Authors: George Binsah , Jabbour Elias , Cabrero Monica , Jain Nitin , Daver Naval , Ravandi Farhad , Borthakur Gautam , Bohannan Zach , Cortes Jorge E. , Keating Michael J , O'Brien Susan , Kantarjian Hagop M. , Garcia-Manero Guillermo 
Published: October 2019

Abstract
Background: AML-M6 is a subtype of acute myeloid leukemia associated with poor prognosis. Hypomethylating agents (HMA) have not been extensively studied in patients with AML-6.
Objective: To compare HMA therapy to conventional chemotherapy (CT) in patients with AML-6
Method: We reviewed 160 consecutive patients with AML-M6 treated with HMA (n=25) or CT (n=135) between 1980 and 2014. Patient clinical and demographic data were analyzed for contribution to survival and response outcomes.
Results: The median patient age for our patients was 62 years (ranges, 16-87 years). Median follow-up was 56 months (range, 2-269 months). Poor cytogenetics, including complex karyotypes and chromosome 7 alteration, were observed in 96 (60%) patients including 62% of patients in the CT arm and 76% of patients in the HMA arm, respectively (p=0.002). Mean blast percentage was 24% (26% for CT patients versus 15% for HMA patients; p=0.001). ECOG Performance status ≥2 was present in 26 (16%) patients (17% of CT patients versus 16% of HMA patients; p=0.59). Patients who received HMA were older (median age 67 vs 59; p<0.01) and had a poorer karyotype, including complex cytogenetics and chromosome 7 alterations (88% for HMA patients versus 56% for CT patients; p=0.002), whereas patients treated with CT presented with a lower, but not clinically relevant, hemoglobin level and higher bone marrow blast percentage.
Overall, 44% of patients treated with HMA achieved complete remission (CR) versus 66% for those treated with CT (p=0.03). However, there were no significant differences in overall response rate (ORR) for patients treated with CT and HMA (67% vs 56%, respectively; p=0.359). By univariate analysis, variables associated with ORR were age, treatment modality (CT vs HMA), poor cytogenetics, and bone marrow blast percentage. Only poor risk cytogenetics maintained significant impact on multivariate analysis (ORR=0.36 [95% CI: 0.13-0.95]; p=0.039).
Median overall survival (OS) and disease-free survival (DFS) were 10 months (range, 8-12) for and 5 months (range, 3-6) respectively for the whole cohort. The 1-year OS and DFS rates were 39% and 27%, respectively. The 8-week mortality rate for patients treated with HMA and CT were 12% and 20%, respectively. In a Cox-regression multivariate model, variables with independent impact on OS were diagnosis prior to 2000 (HR=1.84 [95% CI: 1.12-3.02]; p = 0.016), age > 62 years (HR=2.03 [95% CI: 1.33-3.08]; p=0.001), CR (HR=0.301 [95% CI: 0.18-0.49]; p=0.000), poor cytogenetics (HR=4.85 [95% CI: 2.96-7.96]; p=0.000), and ECOG performance status ≥2 (HR=2.23 [95% CI: 1.21-4.09]; p=0.01). Considering only patients with complex cytogenetics and chromosome 7 abnormalities, there were no differences in median OS between CT and HMA (5 months vs 6 months; p=0.23)
Conclusion: Our retrospective analysis found that HMA may be a good alternative to CT for patients with AML-M6. Patients treated with HMA had more favorable 1-year OS and DFS as well as lower 8-week mortality rates. These results were despite the fact that most of the patients treated in our HMA group had generally worse prognosis than those in the CT group.

Disclosures
Kantarjian: ARIAD: Research Funding; Pfizer: Research Funding; Amgen: Research Funding.