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Immune-checkpoint inhibitor use in patients with cancer and pre-existing autoimmune diseases

Nature Reviews Rheumatology volume 18, pages 641–656 (2022)Cite this article

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Abstract

Immune-checkpoint inhibitors (ICIs) have dramatically changed the management of advanced cancers. Designed to enhance the antitumour immune response, they can also cause off-target immune-related adverse events (irAEs), which are sometimes severe. Although the efficacy of ICIs suggests that they could have wide-ranging benefits, clinical trials of the drugs have so far excluded patients with pre-existing autoimmune disease. However, evidence is accumulating with regard to the use of ICIs in this ‘at-risk’ population, with retrospective data suggesting that they have an acceptable safety profile, but that there is a risk of disease flare or other irAE occurrence. The management of immunosuppressive drugs at ICI initiation in patients with autoimmune disease (or later in instances of disease flare or irAE) remains a question of particular interest in clinical practice, in which there is always a search for the balance between protecting against autoimmunity and ensuring a good tumour response. Although temporary use of immunosuppressants seems safe, prolonged use or use at ICI initiation might hamper the antitumour immune response, prompting clinicians to use the minimal efficient immunosuppressive regimen. However, a new paradigm is emerging, in which inhibitors of TNF or IL-6 could have synergistic effects with ICIs on tumour response, while also preventing severe irAEs. If confirmed, this ‘decoupling’ effect on toxicity and efficacy could change therapeutic practice in this field. Knowledge of the current use of ICIs in patients with pre-existing autoimmune disease, particularly with regard to the use of immunosuppressive drugs and/or biologic DMARDs, can help to guide clinical practice.

Key points

  • Immune-checkpoint inhibitors (ICIs) should be offered to patients with pre-existing autoimmune disease who have advanced cancer, within the process of shared decision-making.

  • High risk of (generally mild) flare (up to 75%) is reported for patients with pre-existing rheumatoid arthritis, polymyalgia rheumatica and psoriatic arthritis following ICI initiation.

  • ICI-mediated immune toxicity is mostly manageable with glucocorticoids, and rarely requires DMARDs in patients with pre-existing autoimmune disease.

  • A minimal immunosuppressive regimen should be reached at ICI initiation, but selective therapies should be used for active and severe pre-existing autoimmune disease.

  • Basic and clinical research are needed to better understand the pathophysiology underlying ICI-induced autoimmune disease flare compared with immune-related adverse events, and to identify predictive factors of immune toxicity.

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Fig. 1: Mechanisms of action of immune-checkpoint inhibitors.
Fig. 2: Factors potentially involved in the pathogenesis of immune-related adverse events.

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Authors and Affiliations

  1. Department of Rheumatology, Brest University Hospital, Brest, France

    Alice Tison & Divi Cornec

  2. B Lymphocytes, Autoimmunity and Immunotherapies, UMR 1227, Brest, France

    Alice Tison, Soizic Garaud & Divi Cornec

  3. Department of Internal Medicine, Hôpital Européen, Marseille, France

    Laurent Chiche

  4. Department of Rheumatology, Bordeaux University Hospital, Bordeaux, France

    Marie Kostine

  5. ImmunoConcEpt, CNRS, UMR 5164, University of Bordeaux, Bordeaux, France

    Marie Kostine

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A.T., S.G., L.C., D.C. and M.K. researched data for the article and made substantial contributions to discussions of the content. A.T., S.G. and M.K. wrote the article. A.T., S.G., L.C., D.C. and M.K. contributed to reviewing and editing of the manuscript before submission.

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L.C. reports consultancy and receipt of an honorarium from Novartis and Bristol Myers Squibb. The remaining authors declare no competing interests.

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Nature Reviews Rheumatology thanks A. Bass, L. Cappelli and M. Suarez-Almazor for their contribution to the peer review of this work.

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Tison, A., Garaud, S., Chiche, L. et al. Immune-checkpoint inhibitor use in patients with cancer and pre-existing autoimmune diseases. Nat Rev Rheumatol 18, 641–656 (2022). https://doi.org/10.1038/s41584-022-00841-0

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