Cutaneous immune-related adverse events (cirAEs) from immune checkpoint inhibitor (ICI) therapy can disrupt the course of oncology treatment. Data guiding the safety and effectiveness of biologic agents for cirAEs remain limited. We therefore aimed evaluate the efficacy and oncologic safety of biologic therapy for ICI-associated cirAEs. We conducted a retrospective chart review of adult patients at Beth Israel Deaconess Medical Center from January 1 st 2015 to July 31 st 2025 who received biologic therapy from a dermatologist for a cirAE while on immunotherapy for a malignancy. We collected demographics, cirAE phenotype, biologic used, cirAE outcomes, ICI treatment course, and cancer status before and after biologic initiation. Twenty-two patients with 30 discrete cirAEs were included. The most common cirAE phenotypes were psoriasiform (36%), immunobullous (29%), and eczematous (26%) erupitons. Overall, 19/22 patients (86%) achieved complete resolution of their cirAE on biologic therapy. Among patients whose ICIs were held or discontinued, 6/18 (33%) successfully resumed immunotherapy after cutaneous improvement on a biologic. No patient experienced a change in cancer status from before to after biologic treatment. Our findings suggest that biologic medications are highly effective for treating a range of ICI-induced cirAEs. Furthermore, their use appears safe in this population, with no adverse impact on cancer status. Biologic therapy may allow for the salvage of ICI treatment in a subset of patients, potentially improving overall cancer outcomes.
Short Report
Biologic Treatment for Cutaneous Immune-Related Adverse Events in Cancer Patients Undergoing Immune-Checkpoint Therapy: A Retrospective Review
https://doi.org/10.21203/rs.3.rs-8065496/v1
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immune-related adverse event
biologics
immune-checkpoint inhibitors (ICI)
immunotherapy toxicity
Immunotherapy has become a pillar of oncologic care. While revolutionary for the treatment of many different solid organ tumors, immune checkpoint inhibitors (ICIs) induce cutaneous immune-related adverse events (cirAEs) in 30-60% of patients [1]. Some of these reactions are severe and may halt cancer therapy. Dermatologists play a critical role in the care of cancer patients experiencing cirAEs, both to reduce patient suffering and to salvage cancer treatment. While traditional teaching and medication package inserts advise against the use of biologic medications to treat skin conditions in patients with active malignancy, these medications may be effective in the treatment of cirAEs. The use of biologics to treat cirAEs and the impact on cancer therapy outcomes are being increasingly explored [2-3]. Our research aims to assess: 1) the efficacy of biologic therapies in the treatment of ICI-related cirAEs and 2) safety of using biologic therapies in cancer patients with respect to their ICI treatment response and cancer status.
We conducted an electronic medical record query for all adult patients on biologic medication, who had at least one visit with the Hematology and Oncology Department at Beth Israel Deaconess Medical Center (BIDMC) between January 1st 2015 and July 31st 2025. We used the following inclusion criteria: 1) at least 1 malignancy diagnosis that was treated with immunotherapy 2) documented cirAE assessed by Dermatology 3) prescription of biologic medication by Dermatology to treat cirAE, and 4) both oncologic and dermatologic care provided at BIDMC between January 1st 2015 and January 31st 2025. We collected and analyzed data including demographics, cancer type, cirAE type, specific biologic medication prescribed for cirAE, treatment response for cirAE (complete, partial, or no response), cancer treatment (i.e., ICI) response, and cancer status. We classified outcomes for cancer treatment response and cancer status based on medical oncology documentation as follows. Cancer treatment response was classified as complete response (no detectable disease), partial response (reduced disease burden), stable disease (no significant change), or progressive (worsening or new disease). Cancer status was classified as remission/stable disease (includes both complete remission, partial remission, and stable disease) or progressive disease (increasing cancer burden) based on the most recent oncologic visit note. Additionally, we recorded cancer status of all patients before and biologic treatment.
A total of 22 patients were included. Seven patients had multiple cirAEs, resulting in a total of 30 discrete cirAEs. Psoriasiform eruptions were the most prevalent cirAE (36%), followed by immunobullous eruptions (29%) and eczematous eruptions (26%) (Table 1). Immunotherapy agents causing cirAEs included pembrolizumab, nivolumab, durvalumab, cemipilimab, zimberelimab, and dostarlimab. Lung cancer (27%) and renal cell carcinoma (18%) were the most common cancer types. Nineteen of 22 patients (86%) achieved complete resolution of cirAE with biologic therapy; 1 patient expired before dermatology follow-up, and 2 patients failed biologic therapies for cirAE treatment. Out of 19 patients who had ICI either temporarily held or discontinued, six patients were able to resume immunotherapy, which had been held in the setting of cirAEs, after cirAEs improved on biologic therapy (Table 1). One patient was resumed on ICI therapy due to progression of their cancer. Twelve patients discontinued immunotherapy permanently after rash onset for reasons unrelated to the rash or rash treatment response – three as part of transition to palliative care, five in the setting of no evidence of disease on re-imaging, two due to other non-cutaneous adverse events, and two due to failure of ICI. None of the 22 patients had any change in cancer status, starting with 1) immediately after initiation of ICI therapy, 2) during biologic therapy, and ending with 3) as per the most recent oncologic assessment before the end of our search date (Table 2).
Our findings suggest the superior efficacy of biologics in treating cirAEs during immunotherapy, as an overwhelming majority (86%, or 19/22) of our patients experienced complete resolution of their eruptions. Our data also supports the relative safety of using of biologics to manage cirAEs in cancer patients, as all of our patients did not have a change in cancer status from before to after biologic treatment. These findings align with prior studies that report cancer patients treated with biologics for ICI-induced bullous pemphigoid did not show a pattern of worsening cancer progression or reducing tumor response rates [2]. Our work also supports research demonstrating comparable rates of new or recurrent malignancy in patients with history of cancer on biologics compared to traditional immune-modulating agents for inflammatory conditions [4-5]. Preclinical translational models provide mechanistic support in that specific cytokine blockade, for example, that of IL-17RA, reduced organ-infiltrating lymphocytes and skin inflammation, while also maintaining or even enhancing antitumor CD8+ T cell activity, suggesting that this approach can dissociate toxicity from antitumor efficacy [6]. Lastly, 33% (6/18) of our patients who had discontinued ICI were restarted on ICI due to skin improvement. Perhaps utilization of biologic medications to treat cirAEs would allow for more ICI salvage, thereby potentially improving cancer outcomes [7-8]. Our findings underscore the dual advantages of biologic medications in cancer patients on ICIs. The medications are highly effective, and they appear not to impact cancer outcomes. Further studies with larger patient cohorts are necessary to validate these findings and to support earlier initiation of biologic treatments of cirAEs both to reduce patient suffering and to salvage cancer therapy.
Funding sources: None
Conflicts of Interest: None declared.
IRB approval status: Reviewed and approved by BIDMC IRB
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Table 1. Type of cirAEs, Biologic agents used, and Immunotherapy Treatment Course after cirAE Onset
Table 2. ICI Treatment Response and Cancer Status
†Cancer status was classified as defined by the most recent oncologic visit
*Observation/no treatment; expired while receiving treatment
**Expired during treatment; not yet started treatment
No competing interests reported.