Increased plasma imatinib exposure and toxicity in chronically treated GIST patients with SARS-CoV-2 infection: a case series.

Autor: Gagno S; Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy., Posocco B; Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy., Orleni M; Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy., Cecchin E; Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy., Fumagalli A; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy., Guardascione M; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy., Buonadonna A; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy., Polesel J; Unit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy., Puglisi F; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.; Department of Medicine, University of Udine, Udine, UD, Italy., Toffoli G; Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy., Cecchin E; Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2024 Oct 09; Vol. 15, pp. 1441620. Date of Electronic Publication: 2024 Oct 09 (Print Publication: 2024).
DOI: 10.3389/fimmu.2024.1441620
Abstrakt: Introduction: Inflammatory factors released during severe coronavirus disease-19 (COVID-19) caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are known to influence drug exposure, but data on the effect of mild infection are few. Here we describe for the first time an increase in plasma imatinib and norimatinib concentrations observed in a series of 5 patients treated with imatinib for gastrointestinal stromal tumor (GIST) after mild COVID-19.
Methods: The patients were undergoing routine therapeutic drug monitoring (TDM) and pharmacogenetic (PGx) analyses of polymorphisms in genes involved in imatinib metabolism and transport ( CYP3A4 , CYP3A5 , ABCB1 , and ABCG2 ) when SARS-CoV-2 infection occurred. Imatinib and its active metabolite norimatinib concentrations were determined at C trough using a validated LC-MS/MS method. PGx analyses were performed by KASP genotyping assays on a Real-Time PCR system. All patients received imatinib 400 mg/day. Case 1 was prospectively monitored. Cases 2-5 were identified retrospectively.
Results: On average, imatinib C trough increased significantly by 70% during COVID-19, whereas norimatinib showed a 44% increase compared with pre-COVID-19 levels. Elevated plasma imatinib concentrations persisted up to 6 months after infection remission. In 3 cases, this increase reflected the occurrence or worsening of imatinib side effects.
Conclusion: This case-series highlights the clinical impact of SARS-CoV-2 infection on the management of patients with GIST treated with imatinib.
Competing Interests: Author FP has received honoraria from Amgen - Astrazeneca - Daiichi Sankyo - Celgene - Eisai - Eli Lilly- - Exact Sciences- Gilead - Ipsen - Italfarmaco - Menarini- MSD - Novartis - Pierre Fabre - Pfizer - Roche - Seagen - Takeda - Viatris. Author FP is currently receiving research funding from Astrazeneca, EISAI, Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
(Copyright © 2024 Gagno, Posocco, Orleni, Cecchin, Fumagalli, Guardascione, Buonadonna, Polesel, Puglisi, Toffoli and Cecchin.)
Databáze: MEDLINE
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