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Hypertransaminasemia in cancer patients receiving immunotherapy and immune-based combinations: the MOUSEION-05 study

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Abstract

Background

The antitumor efficacy of immune checkpoint inhibitors (ICIs) has increasingly emerged during the last few years. However, there is a need to identify the safety profile of these agents more comprehensively, including liver toxicity.

Materials and methods

Herein, we performed a meta-analysis to assess the risk of all-grade and grade 3–4 hypertransaminasemia in cancer patients receiving ICIs—as monotherapy or in combination with other anticancer agents. All the relevant trials were retrieved through EMBASE, Cochrane Library, and PubMed/Medline databases; eligible studies were selected according to PRISMA statement. The pooled relative risk (RR) and 95% confidence interval (CI) were extracted.

Results

Fifty-nine studies were included. The pooled RRs for all-grade AST and ALT increase were 1.45 (95% CI 1.26–1.67) (Supplementary Fig. 3) and 1.51 (95% CI 1.29–1.77) in patients receiving ICIs monotherapy and immune-based combinations compared to control treatment, respectively. The pooled RRs for grade 3–4 AST and ALT increase were 2.16 (95% CI 1.77–2.64) and 2.3 (95% CI 1.91–2.77).

Conclusions

According to our results, ICIs monotherapy and immune-based combinations were associated with higher risk of all-grade and grade 3–4 hypertransaminasemia. Monitoring liver function should be recommended in cancer patients treated with ICIs monotherapy or immune-based combination, and in case of underlying liver disease, a careful risk–benefit assessment appears as a mandatory need.

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  1. Matteo Santoni and Francesco Massari equally contributing to this work.

Authors and Affiliations

  1. Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Istituto Tumori Giovanni Paolo II-Bari, Viale Orazio Flacco 65, 70124, Bari, Italy

    Alessandro Rizzo

  2. Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni-15, 40138, Bologna, Italy

    Veronica Mollica, Valentina Tateo, Elisa Tassinari, Andrea Marchetti, Matteo Rosellini & Francesco Massari

  3. Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138, Bologna, Italy

    Veronica Mollica, Valentina Tateo, Elisa Tassinari, Andrea Marchetti, Matteo Rosellini & Francesco Massari

  4. Department of Surgical Oncology, IRCCS Istituto Tumori ‘Giovanni Paolo II’, Viale Orazio Flacco, 65, 70124, Bari, Italy

    Raffaele De Luca

  5. Oncology Unit, Macerata Hospital, Macerata, Italy

    Matteo Santoni

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A.R. wrote the main manuscript text and performed the statistical analysis. A.R. prepared figures 1-5 and table 1. V.M., V.T., E.T., A.M., and M.R. contributed to data acquisition. V.M., R.D.L., M.S., and F.M. contributed to the conception, design, and manuscript revision. All authors approved the final version of the manuscript.

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Rizzo, A., Mollica, V., Tateo, V. et al. Hypertransaminasemia in cancer patients receiving immunotherapy and immune-based combinations: the MOUSEION-05 study. Cancer Immunol Immunother 72, 1381–1394 (2023). https://doi.org/10.1007/s00262-023-03366-x

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