(030) Characterizing the Incidence of Arsenic Trioxide Holds and Modifications in Patients with Low Risk Acute Promyelocytic Leukemia and Comorbid Obesity

Poster Abstract: Background
Acute promyelocytic leukemia (APL) is a rare leukemia subtype that accounts for an estimated 10-15% of acute myeloid leukemia cases [1]. APL is associated with a high risk of early mortality due to coagulopathic complications, thus highlighting the need for urgent treatment initiation [2]. Although APL was once one of the most lethal forms of acute leukemia, the discovery of all-trans retinoic acid and arsenic trioxide (ATO) have revolutionized the treatment of APL, with complete remission and long-term overall survival rates exceeding 90% [1]. There is currently limited guidance for dosing ATO in patients with obesity, with many institutions using actual body weight to calculate doses without dose capping. Prior studies have yielded inconsistent results regarding the impact of obesity on ATO dose holds and modifications [3,4].

Objectives
This project aims to characterize the incidence of ATO dose holds and modifications in patients with low-risk APL. These rates will be compared between patients with a normal BMI and those with obesity.

Methods
This study is a retrospective chart review of patients with low-risk APL who received any dose of ATO during treatment induction while inpatient at the University of Washington Medical Center – Montlake. Patients with high-risk APL will be excluded. Patients will be stratified by body mass index (BMI), with a BMI of ≥30 kg/m2 classified as obesity per Centers for Disease Control and Prevention definitions. The primary outcome of this study is to classify the incidence of ATO dose holds or modifications during APL induction therapy due to adverse effects, such as QTc prolongation and hepatotoxicity. Secondary outcomes include the incidence of torsade de pointes, incidence of differentiation syndrome, and the rate of complete remission after induction.

Results
Results are pending.

Discussion/Conclusion
Overall, this study will allow for a better understanding if APL patients with comorbid obesity are at a higher risk of therapy-induced toxicity, leading to more dose holds or modifications.

References (must also be included in final poster): [1] Yilmaz M, Kantarjian H, Ravandi F. Acute promyelocytic leukemia current treatment algorithms. Blood cancer journal. 2021;11(6):123.
[2] Abedin S, Altman JK. Acute promyelocytic leukemia: preventing early complications and late toxicities. Hematology 2014, the American Society of Hematology Education Program Book. 2016;2016(1):10-5.
[3] Hickey E, Clemons B, Griffin S, et al. Multicenter evaluation of arsenic trioxide dosing in obese patients with low-intermediate risk acute promyelocytic leukemia. Leuk Lymphoma. 2019;60(14):3557–3560. 
[4] Barsoum B, Henneman A, Ahmad S, et al. Evaluation of the efficacy and safety of arsenic trioxide dosing in obese patients with acute promyelocytic leukemia. Leuk Lymphoma. 2021;62(3):703-708.