Change in cardiac function with CPX-351 in relapsed pediatric AML: A Children’s Oncology Group (COG) report from AAML1421.

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10532 Background: Anthracyclines (AC) are highly effective in treating acute myeloid leukemia (AML), but limited by cardiotoxicity (CTX). CPX-351, a liposomal preparation of daunorubicin (DNR) and cytarabine, may provide therapeutic benefit with less CTX. We evaluated acute changes in cardiovascular (CV) function and biomarkers after 1 cycle of CPX-351 in children with relapsed AML within the phase 1/2 study, AAML1421. Methods: Patients (pts) received 135 units/m2/dose of CPX-351 on days 1, 3, and 5. Echocardiograms were centrally quantified at baseline (BL) and day 29 (end of cycle (EOC)). High sensitivity troponin (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at BL and days 5, 8, 15, 22, and 29. Differences between BL and post-CPX-351 echo/biomarker measurements were analyzed using pre-specified Wilcoxon signed rank tests. The relationship between EOC ejection fraction (EF) and clinical variables was assessed using repeated measures linear regression. Results: In 32 included pts, the median AC exposure prior to study entry was 337 mg/m2 DNR equivalents. At baseline, markers of CV function and stress were abnormal (Table). Over 1 cycle, there was a statistically significant decrease in EF and circumferential strain (Table). NT-proBNP and cTnT did not increase significantly over time. In multivariable analysis, only increasing body surface area was significantly associated with lower EOC EF (b:-5.9, 95% CI -10.8,-0.9). Cancer therapy–related cardiac dysfunction, defined as ≥10% decline in EF to < 50%, occurred in 6/32 pts at EOC. Conclusions: In this single arm study of AC pre-treated children, baseline abnormalities in CV function were common. CPX-351 was associated with a statistically significant decline in CV function without a rise in cardiac biomarkers. Absent a comparator population, it is not known how these cardiac trends compare to non-liposomal AC or non-AC salvage regimens. The COG AAML1831 trial will determine if CPX-351 offers cardioprotection compared to standard AC in pts with de novo AML. Clinical trial information: NCT02642965. [Table: see text]