Introduction: Azacitidine and Venetoclax was approved for older patients in 2020 ineligible for intensive chemotherapy, and it has become an effective standard frontline therapy (DiNardo, et al NEJM 2020.). The relative ease of administration, efficacy, and favorable side-effect profile have allowed patients with AML to be managed closer to home in a community setting with Venetolcax-based regimens. As Venetoclax has become more commonplace in frontline strategies, we sought to evaluate Venetoclax utilization patterns and efficacy in this setting. To assess the impact and tolerance of Venetoclax on AML outcomes in our population, we performed a retrospective cohort study within our treatment network in the greater Memphis area, an area with high levels of poverty complex social determinants of health. Methods: We performed a retrospective cohort study involving data collected from two cancer centers in Memphis, TN from January 2017 to March 2023. Inclusion criteria were patients aged 18-85 diagnosed with either AML or high-grade MDS (ICC defined subsets equivalent to AML) and in receipt of Venetoclax-based therapies. Adverse events were graded based on CTCAE criteria. Out of 515 patients with AML reviewed, 98 patients met the study inclusion criteria. Of the 98 patients, data regarding first vs second regimen Venetoclax utilization was available for 57 patients. For simple comparative analysis, Fischer exact test was performed. Results: The median age at diagnosis was 64 years (range 21-86). 47% patients were female gender. 24.5% of patients were Black or African-American, 71.4% were White, 1% were Asian, and 3.1% were more than one race. This cohort is representative of a real-world population with an average of 1.7 co-morbidities per case. In regard to WHO classification, 6.7% had CBF- AML, , 7.9% AML/MDS-related, 12.4% AML with NPM1 mutation, 4.5% AML with CEBPA mutation, 16.9% AML with other defined alterations, 14.6% AML NOS, 9% Mixed lineage/ambiguous, 2.2% AML with Germlines predisposition (including DDX41), 7.9% Therapy related AML, 11.2% MDS/AML with blasts of 11-20%, and 6.7% were MDS/AML with biallelic TP53. 21% had good risk cytogenetics, 45.7% had intermediate, and 33.3% had poor cytogenetics. Regarding ELN risk categories, 13.2% of patients were characterized as good risk, 48.7% were intermediate, and 38.2% were classified as poor risk. Of the 57 patients, 42 patients (73.6%) received Venetoclax in the first regimen, and 15 patients (23.6%) received Venetoclax in the second. In first line setting, 22 patients (52.3%) received Venetoclax with azacitidine, 17 patients 40.1% received decitabine, 2 patients (4.8%) with cladribine and cytarabine, and 2 patients (4.8%) received Venetoclax alone. 41.4% of patients had a complete response (CR), 27.6% of patients had partial responses, and 31% of patients had a non-response. In a race-based analysis, 47.4% of Caucasian patients had a CR compared to 22.2% of African-American patients with a p value of .01. In the second line setting, Venetoclax was used in 15 patients. 6 patients (40%) received azacitidine with venetcloax, 6 patients (40%) received decitabine, 1 patient (6.7%) received cytarabine, 1 patient (6.7%) received enasidenib, and one patient (6.7%) received nelarabine, cyclophosphamide, and cytarabine. A similar trend was observed with 41.3% of patients had a CR, 37% had other type of or partial response, and 21.7% had a non-response. Regarding complications, 32.1% of patients developed febrile neutropenia, 7.3% liver failure, 5.6% of kidney failure, 1.8% TLS, and 47.3% had prolonged cytopenias. Race-based analysis found no significant difference in treatment-related complications between African-American and Caucasian patients. Conclusion: This retrospective cohort study of 98 patients in Memphis, TN diagnosed with either AML or MDS and treated with a Venetoclax-based regimen highlights the various disease entities per WHO classification that can be treated with such regimens. For patients who are unabe to tolerate nor are good candidates for 7+3, Venetoclax-based regimens provide an alternative treatment option, particularly in the community-based setting. 41.4% of patients had a CR with their first treatment regimen in this cohort. The race-based analysis highlights the importance of inclusion of minority populations in future studies and the need for further research at-large in the community-based setting for Venetoclax-based regimens.

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2025
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