Evaluating Acute Myeloid Leukemia Induction Regimens in Elderly Patients with Unfavorable Risk Cytogenetics That Are Candidates for Intensive Remission Therapy
Authors: Tadros Monica , Koehne Guenther , Zahra Talia , Unzaga Jessica , Shwin Moe , Chow Nicholas 
Published: November 2020

Background/purpose: Standard acute myeloid leukemia (AML) induction regimens have reduced response in elderly patients. As an alternative, hypomethylating agents have better tolerability, but poorer response rates. Venetoclax, an oral anti-apoptotic protein BCL-2 inhibitor, was approved in combination for the treatment of newly-diagnosed AML adults 75 years or older and is supported by NCCN guidelines in combination with hypomethylating agents or low dose cytarabine for special patient populations. This study evaluated the outcomes of AML induction regimens in unfavorable risk patients 60 years old or older that were candidates for intensive remission induction therapy.
Methodology: This was an IRB-approved retrospective chart review of AML patients with unfavorable risk cytogenetics aged 60 or older admitted to the Baptist Hospital of Miami Oncology Unit between February 1st, 2018 and August 1st, 2019, an 18-month period. Patients were included if they received one of the following AML induction regimens: daunorubicin + cytarabine (7+3), liposomal daunorubicin/cytarabine (CPX-351), venetoclax + decitabine (VEN +DEC), venetoclax + azacitidine (VEN+ AZA), or venetoclax + low dose cytarabine (VEN + LoDAC). For the purpose of the study, the 7+3 and CPX-351 regimens were classified as high intensity, while the VEN+ DEC, VEN+AZA, and VEN+LoDAC regimens were classified as low intensity. The primary outcome assessed was the rate of complete morphologic remission (CR) and complete morphologic remission with incomplete count recovery (CRi). Additional secondary outcomes included rate of induction failure, relapse free survival (RFS), time to complete remission, transplant status and eligibility, length of stay (LOS), and incidence of any-grade treatment-related toxicities.
Results: A total of 20 patients were identified. Of the 20 patients, 9 (45%) received induction with 7+3, 3 (15%) received CPX-351, 5 (20%) received VEN+DEC, and 3 (15%) received VEN +AZA, thus 12 (60%) received high intensity regimens, while 8 (40%) received low intensity. The primary outcome of CR/CRi rate was 75% in the high intensity group vs. 63% in the low intensity group (P=0.0922). Furthermore, the rate of induction failure, median time to CR/CRi, median LOS, and transplant eligibility were similar between the high and low intensity groups. The median RFS was 272 days in the high intensity groups vs. 223 days in the low intensity groups (P=0.1496). The median duration of neutropenia was 30 days in the high intensity group vs. 34 days in the low intensity group while the median duration of thrombocytopenia was 31 days in the high intensity groups vs. 32 days in the low intensity group. Finally, the rate of grade 3 and 4 toxicities was 100% in the high intensity group vs. 88% in the low intensity group (P=0.0003), with higher incidences of grade 3 febrile neutropenia, grade 4 thrombocytopenia, and grade 1 and 2 liver enzyme elevations noted in the high intensity group.
Conclusion: There were no statistically significant differences between the CR/CRi rates and median RFS of the high and low intensity groups, while there were significantly less grade 3 and 4 toxicities noted in the low intensity group. Venetoclax-based regimens are an acceptable alternative to intensive induction therapy in unfavorable risk patients over the age of 60 due to similar outcomes and less toxicity.

Disclosures
No relevant conflicts of interest to declare.