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Cardiotoxicity of CPX-351 in children and adolescents with relapsed AML: a Children's Oncology Group report.
Leger, Kasey J; Absalon, Michael J; Demissei, Biniyam G; Smith, Amanda M; Gerbing, Robert B; Alonzo, Todd A; Narayan, Hari K; Hirsch, Betsy A; Pollard, Jessica A; Razzouk, Bassem I; Getz, Kelly D; Aplenc, Richard; Kolb, E Anders; Ky, Bonnie; Cooper, Todd M.
Afiliación
  • Leger KJ; Division of Pediatric Hematology/Oncology, Seattle Children's Hospital, University of Washington, Seattle, WA, United States.
  • Absalon MJ; Department of Pediatrics, Oregon Health Sciences University, Portland, OR, United States.
  • Demissei BG; Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
  • Smith AM; Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
  • Gerbing RB; Children's Oncology Group, Monrovia, CA, United States.
  • Alonzo TA; Children's Oncology Group, Monrovia, CA, United States.
  • Narayan HK; Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, United States.
  • Hirsch BA; Department of Pediatrics, University of California San Diego, Rady Children's Hospital San Diego, La Jolla, CA, United States.
  • Pollard JA; Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States.
  • Razzouk BI; Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, United States.
  • Getz KD; Department of Pediatrics, Harvard Medical School, Boston, MA, United States.
  • Aplenc R; Department of Pediatrics, Peyton Manning Children's Hospital at Ascension St. Vincent, Indianapolis, IN, United States.
  • Kolb EA; Departments of Biostatistics, Epidemiology & Informatics and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
  • Ky B; Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, United States.
  • Cooper TM; Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Front Cardiovasc Med ; 11: 1347547, 2024.
Article en En | MEDLINE | ID: mdl-38947228
ABSTRACT

Introduction:

Anthracyclines are effective in treating acute myeloid leukemia (AML) but limited by cardiotoxicity. CPX-351, a liposomal daunorubicin and cytarabine, may provide therapeutic benefit with less cardiotoxicity. Acute changes in left ventricular systolic function and cardiac biomarkers were evaluated after a cycle of CPX-351 in children with relapsed AML treated on the phase 1/2 Children's Oncology Group study, AAML1421.

Methods:

Subjects received 135 units/m2/dose of CPX-351 on days 1, 3, and 5 as cycle 1. Echocardiograms were performed and centrally quantitated at baseline and at the end of cycle 1 (day 29 +/- 1 week). High sensitivity troponin (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at baseline and serially through the end of cycle 1 (days 5, 8, 15, 22 and 29). Differences between baseline and post-CPX-351 echo/biomarker measures were analyzed using Wilcoxon signed rank tests. Linear regression was used to model post-CPX-351 left ventricular ejection fraction (LVEF) with cTnT/NT-proBNP at each time point, controlling for baseline LVEF. Cancer therapy related cardiac dysfunction (CTRCD) was defined as a decline in LVEF of ≥10%-<50%.

Results:

Twenty-five of 38 heavily anthracycline pre-treated (median 348 mg/m2 daunorubicin equivalents) subjects enrolled on AAML1421 were included in the cardiac analyses. At baseline, centrally quantitated LVEF was <50% in 8 of 25 subjects (32%) with a median LVEF of 53.8% [48.0, 56.9]. Following CPX-351, LVEF declined significantly (ΔLVEF -3.3% [-7.8, 0]) and 6 of 25 subjects (24%) experienced CTRCD. Amongst all subjects, hs-cTnT was modestly increased at end of cycle 1 compared to baseline [baseline hs-cTnT 7.2 (3, 10.6); ΔcTnT 1.80 (0, 6.1), p = 0.03]. NT-proBNP remained stably elevated without significant change. No significant associations were seen between NT-proBNP or cTnT levels and post-CPX-351 LVEF.

Discussion:

In this single arm study of anthracycline pre-treated children exposed to CPX-351, baseline abnormalities in cardiovascular function were prevalent. Following CPX-351, LVEF decreased, cTnT increased, and NT-proBNP did not change. Longer follow-up is needed to determine whether these changes result in clinically meaningful long-term decrements in cardiac function. An ongoing randomized trial of CPX-351 compared to standard anthracyclines in anthracycline naïve patients will provide further insight into the cardiac effects of CPX-351 (ClinicalTrials.gov; NCT04293562).
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Cardiovasc Med Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Cardiovasc Med Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza