Abstract 4373: Venetoclax-based therapy in treatment-naïve and relapsed/refractory acute myeloid leukemia
Authors: Ravindra Aditya , Acharya Luna , Loeffler Bradley , Bell Sarah L. , Sutamtewagul Grerk , Dhakal Prajwal 
Published: April 2023

Abstract
Background: Clinical trials in acute myeloid leukemia (AML) report complete remission (CR) in ~60% of newly diagnosed (ND) pts treated with venetoclax (VEN)-based therapy with hypomethylating agents (HMA, azacitidine [AZA] and decitabine [DEC]) or low-dose cytarabine. However, results from prospective studies in relapsed refractory (R/R) AML remain scarce. Here, we compare the outcomes in ND and R/R pts treated with VEN-based therapy.
Methods: We performed a retrospective analysis of ND and R/R pts with AML diagnosed between 2016 and 2021 who were treated with VEN-based therapy at the University of Iowa. We used ANOVA and chi-square test to compare variables between ND and R/R pts. Logistic regression analyses and Cox regression models evaluated the effects of ND vs. R/R AML on objective response rate (ORR defined as complete remission (CR) + complete remission with incomplete count recovery [CRi]) and overall survival (OS), respectively. OS was estimated using the Kaplan-Meier method.
Results: Of 53 pts, 31 pts had ND AML, and 22 pts had R/R AML. Median age was 67 years (range 26-85). Among total pts, 52% were treated with VEN + AZA, 48% were treated with VEN+ DEC, 25% had prior exposure to HMA, and 19% had an allogeneic transplant before treatment with VEN-based therapy. Eleven pts had TP53 mutation (7 pts in ND, 4 in R/R group), 13 had NPM1 mutation (ND- 8, R/R-5), and 7 had FLT3 mutation (ND-5, R/R-2). ORR was 53% in total pts (CR- 34%, CRi- 19%), of which 11% did not have minimal residual disease. There was no statistically significant difference in ORR between ND and R/R pts (Odds ratio [OR] 2.04, 95% confidence interval [CI] 0.6-6.4, p=0.2). Treatment with VEN + DEC conferred a similar ORR compared to VEN + AZA (OR 0.37, 95% CI 0.1-1.2, p=0.1). Prior HMA use did not affect ORR (OR 0.4, 95% CI 0.08-2.2, p=0.3). ND pts had longer 6-month OS than R/R pts (82% vs. 55%), but 12-month OS was similar (59% vs. 55%). ND or R/R status did not affect OS (Hazard ratio [HR] 0.7, 95% CI 0.3-1.6, p=0.4). Treatment with VEN + DEC conferred similar OS compared to VEN + AZA (HR 1.6, 95% CI 0.7-3.7, p=0.2). Age, TP53, NPM1, and FLT3 mutations, and adverse cytogenetics, did not affect ORR or OS.
Conclusions: Our real-world analysis shows no significant difference in ORR or OS among pts with ND or R/R AML indicating effective response to VEN-based therapy regardless of treatment status. We report similar 12-month OS for ND and R/R pts despite a higher 6-month OS for ND group. Treatment combination with either AZA or DEC had comparable outcomes, and prior HMA use did not predict worse outcomes in our study. These results are important clinically as AZA and DEC are often used interchangeably, and a significant proportion of pts with prior myelodysplastic syndrome are treated with HMA. Subsequent studies are required to understand the similarities and differences in factors predicting response to VEN-based therapy in ND and R/R AML.
Citation Format: Aditya Ravindra, Luna Acharya, Bradley Loeffler, Sarah L. Bell, Grerk Sutamtewagul, Prajwal Dhakal. Venetoclax-based therapy in treatment-naïve and relapsed/refractory acute myeloid leukemia. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4373.