Treatment discontinuation due to toxicity for patients with acute myeloid leukemia (AML) treated on SWOG S1203.

6529 Background: Curative-intent therapy for patients with newly diagnosed AML centers on the use of cytarabine as part of an intensive multi-drug induction regimen. Treatment-related toxicity may lead to patients stopping treatment, despite the considerable risk of inadequately treated AML. We compared rates of protocol therapy discontinuation due to adverse events (AEs) in either of two standard induction regimens (7+3 or high dose cytarabine + idarubicin, IA) on the S1203 study (Garcia-Manero; Leukemia 2023). Methods: S1203 was a randomized study of patients 45%, and no prolonged QTc interval or known cardiac disease. There were no exclusion criteria for kidney or liver function. On the 7+3 induction arm, subjects received daunorubicin 90 mg/m 2 IV daily days 1-3 with continuous infusion cytarabine 100 mg/m 2 daily days 1-7. On the IA arm, subjects received idarubicin 12 mg/m 2 daily days 1-3 with continuous infusion cytarabine 1.5 g/m 2 daily days 1-4. Toxicities were assessed per the Common Terminology Criteria for Adverse Events version 4.0. Rates of discontinuation were compared using Fisher’s exact test. Results: From 4/2013-11/2015, 522 subjects were randomized (261 to each arm). Treatment discontinuation due to either death or toxicity occurred in 8 vs 22 patients on 7+3 vs IA respectively (p=0.014). During induction, 0 patients on the 7+3 arm discontinued treatment due to toxicity versus 4 patients on the IA arm (0% vs 2%; p=0.12). Toxicities leading to treatment discontinuation on the IA arm included congestive heart failure (n=2, one with concurrent arrhythmia), acute kidney injury (n=1), and hypotension complicated by stroke and cardiac arrest (n=1). Two of the 4 patients who discontinued treatment due to toxicity on IA achieved a complete remission after their first cycle. For patients with PS 2-3 (n=40 on 7+3, n=27 on IA), rates of grade 3-5 AEs were 85% vs 86% and rates of grade 5 AEs were 0% vs 11% (p=0.065). Conclusions: 7+3 was well tolerated. Excluding patients from S1203 with PS 2-3 or decreased hepatic/renal function would not have prevented treatment-related toxicity. The low rate of protocol therapy discontinuation due to toxicity suggests that eligibility criteria for clinical trials could be further broadened to improve patient access. Clinical trial information: NCT0180233 . Table: see text