Systemic Treatment of Cutaneous Adverse Events After Immune Checkpoint Inhibitor Therapy: A Review

Brown, Alexandria; Masterson, Wylie; Lo, Jonathan; Patel, Anisha B.

doi:10.1097/der.0000000000000776

Cited by 5 publications

(2 citation statements)

References 78 publications

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“…Similar considerations could apply in respect of IL-6 targeting, another increasingly popular approach ( 103 ). B-cell depletion with the anti-CD20 monoclonal antibody rituximab has shown some promise for dermatological irAEs, with no apparent adverse impact on survival ( 104 ), and observations in inflammatory arthritis reviewed above arguably support interest in the approach. This should, however, be balanced against the general dearth of infiltrating B-cells in irAE tissues described herein, together with very recent data indicating that regulatory B-cells (Bregs), which would also be targeted by an anti-CD20 strategy, may play a critical role in the prevention of irAEs ( 105 ).…”

Section: Conclusion and Therapeutic Considerationsmentioning

confidence: 99%

Immune-related adverse events in checkpoint blockade: Observations from human tissue and therapeutic considerations

et al. 2023

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Checkpoint inhibitors (CPIs) are monoclonal antibodies which, by disrupting interactions of immune checkpoint molecules with their ligands, block regulatory immune signals otherwise exploited by cancers. Despite revolutionary clinical benefits, CPI use is associated with an array of immune-related adverse events (irAEs) that mirror spontaneous autoreactivity. Severe irAEs necessitate pausing or stopping of CPI therapy and use of corticosteroids and/or other immunomodulatory interventions. Despite increasingly widespread CPI use, irAE pathobiology remains poorly understood; its elucidation may point to targeted mitigation strategies and uncover predictive biomarkers for irAE onset in patients, whilst casting new light on mechanisms of spontaneous immune-mediated disease. This review focuses on common CPI-induced irAEs of the gut, skin and synovial joints, and how these compare to immune-mediated diseases such as ulcerative colitis, vitiligo and inflammatory arthritis. We review current understanding of the immunological changes reported following CPI therapy at the level of peripheral blood and tissue. Many studies highlight dysregulation of cytokines in irAE-affected tissue, particularly IFNγ and TNF. IrAE-affected tissues are also predominantly infiltrated by T-cells, with low B-cell infiltration. Whilst there is variability between studies, patients treated with anti-programmed cell death-1 (PD-1)/PDL-1 therapies seem to exhibit CD8+ T-cell dominance, with CD4+ T-cells dominating in those treated with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) monotherapy. Interestingly, CD8+CXCR3+ T-cells have been reported to be elevated in gastrointestinal, dermatological and musculoskeletal -irAE affected tissues. These findings may highlight potential opportunities for therapeutic development or re-deployment of existing therapies to prevent and/or improve the outcome of irAEs.

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Section: Conclusion and Therapeutic Considerationsmentioning

confidence: 99%

Immune-related adverse events in checkpoint blockade: Observations from human tissue and therapeutic considerations

et al. 2023

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“…A case report of a patient who received rituximab for the treatment of vasculitis with complete depletion of B-cells, after receiving a PD-1 inhibitor she had adequate tumor response and tolerability ( 61 ). Another retrospective of 10 who received rituximab for the treatment of cutaneous irAEs all had an excellent response, but cancer outcomes were not reported ( 62 ).…”

Section: Biologic Immunosuppressantsmentioning

confidence: 99%

The effects of glucocorticoids and immunosuppressants on cancer outcomes in checkpoint inhibitor therapy

Bruera

Suarez‐Almazor

2022

Front. Oncol.

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The emergence of checkpoint inhibitors has created a paradigm shift for the treatment of various malignancies. However, although these therapies are associated with improved survival rates, they also carry the risk of immune-related adverse events (irAEs). Moderate to severe irAEs are typically treated with glucocorticoids, sometimes with the addition of immunosuppressants as steroid-sparing therapy. However, it is unclear how glucocorticoids and immunosuppressants may impact cancer survival and the efficacy of immune checkpoint therapy on cancer. In this narrative review, we discuss the effects of glucocorticoids and immunosuppressants including methotrexate, hydroxychloroquine, azathioprine, mycophenolate mofetil, tumor-necrosis factor (TNF)-inhibitors, interleukin-6 inhibitors, interleukin-1 inhibitors, abatacept, rituximab, and Janus kinase inhibitors (JAKi) on cancer-specific outcomes in the setting of immune checkpoint inhibitor use.

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The Use of Biologic Agents for the Treatment of Cutaneous Immune-Related Adverse Events from Immune Checkpoint Inhibitors: A Review of Reported Cases

Pach,

Valido,

Belzer

et al. 2024

Am J Clin Dermatol

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Systemic Treatment of Cutaneous Adverse Events After Immune Checkpoint Inhibitor Therapy: A Review

Cited by 5 publications

References 78 publications

Immune-related adverse events in checkpoint blockade: Observations from human tissue and therapeutic considerations

Immune-related adverse events in checkpoint blockade: Observations from human tissue and therapeutic considerations

The effects of glucocorticoids and immunosuppressants on cancer outcomes in checkpoint inhibitor therapy

The Use of Biologic Agents for the Treatment of Cutaneous Immune-Related Adverse Events from Immune Checkpoint Inhibitors: A Review of Reported Cases

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