Hepatotoxicity as dose-limiting toxicity of the combination of bosutinib and atezolizumab in patients with chronic myeloid leukemia. Results of the ZEROLMC study.

Autor: Pérez-Lamas L; Hospital Universitario Doctor José Molina Orosa, Lanzarote, Spain., de Paz Arias R; Hospital Universitario La Paz, Madrid, Spain., Díaz RMA; Hospital Universitario Doce de Octubre, Madrid, Spain., Montero LFC; Hospital Virgen de la Salud, Toledo, Spain., Payer ÁR; Hospital Universitario Central de Asturias, Oviedo, Spain., Sierra M; Hospital Universitario de Salamanca, Salamanca, Spain., Marín FF; Hospital General Universitario Morales Meseguer, CIBERER, UCAM, Murcia, Spain., López RP; Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain., Cirici BX; Institut Català d'Oncologia-Hospital germans Trias i Pujol, Universitat Autònoma de Barcelona, Josep Carreras Leukemia Research Institute, Badalona, Spain., Steegmann JL; Hospital de La Princesa, Madrid, Spain., Gómez Casares MT; Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas, Spain., Martínez-López J; Hospital Universitario Doce de Octubre, Madrid, Spain., García-Gutiérrez V; Hospital Universitario Ramón y Cajal, IRYCIS, Universidad de Alcalá, Madrid, Spain. jvalentingg@gmail.com.
Jazyk: angličtina
Zdroj: Annals of hematology [Ann Hematol] 2024 Oct; Vol. 103 (10), pp. 4045-4055. Date of Electronic Publication: 2024 Apr 03.
DOI: 10.1007/s00277-024-05662-7
Abstrakt: In the field of chronic myeloid leukemia (CML), new strategies are needed to increase the rate of successful treatment discontinuations, a crucial goal in this disease. Anti-PD-L1 checkpoint inhibitors are a promising therapeutic approach in CML after the demonstration of an increase of these inhibitory molecules in patients with CML. A phase Ib/II (NCT04793399, registration date March 11, 2021) open-label exploratory trial has been conducted to evaluate the safety of atezolizumab, a humanized anti-PD-L1 antibody, in combination with bosutinib in patients with newly diagnosed chronic phase CML. A total of 36 patients were planned to be enrolled, but the study had to be prematurely terminated due to safety concerns. Nine patients were included in the study, and only 8 went on to receive the combination with atezolizumab. There were a total of 44 adverse events (AEs) during the study period. The most frequent were gastrointestinal (50%), mostly mild (86% grade 1-2). The most serious AEs were hepatic. There were 17 hepatic AEs in 5 patients. Of the hepatic AEs 5 were during the bosutinib monotherapy phase and 12 during the combination phase (AST increase x4, ALT increase x4, blood bilirubin increase x1, alkaline phosphatase elevation x2, GGT increase x2), most of them grade 3-4. There were 2 patients who presented a dose-limiting toxicity; a grade 3 elevation of transaminases, that led to premature termination of the study. The combination of atezolizumab with bosutinib presents hepatotoxicity as a dose-limiting effect and therefore we do not recommend to explore this combination in future studies.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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