Bispecific Dual-Immune Checkpoint Inhibitor Associated Cutaneous Toxicity - A Report of Lorigerlimab Adverse Skin Reaction in Two Cancer Patients

Sep 22, 2026

Lorigerlimab is a dual bispecific antibody targeting CTLA-4 and PD-1 for advanced solid cancers. Although cutaneous immune-related adverse events (irAEs) are usually manageable, its skin histopathology in dual immune checkpoint blockade has not been well defined. Two patients with metastatic castration-resistant prostate adenocarcinoma developed lichenoid and vacuolar interface dermatitis, with one responding to temporary withholding and corticosteroids and the other requiring complete discontinuation.

LanguageEnglish

CategoryResearch & Report

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Pages5

Reading Time13 min

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Abstract

Introduction

Case Reports

Case 1

Case 2

Journal of Cutaneous Pathology CASE STUDY OPEN ACCESS Bispecific Dual-Immune Checkpoint Inhibitor Associated Cutaneous Toxicity: A Report ofLorigerlimab Adverse Skin Reaction in Two Cancer Patients Niloofar Sina1 | Fiorinda Muhaj2 | Volha Lenskaya3 | Doina Ivan2,3 | Victor G. Prieto2,3 | Jonathan L. Curry3,4 1Department of Pathology, Section of Dermatopathology, University Health Network, University of Toronto, Toronto, Ontario, Canada | 2Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA | 3Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA | 4Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Correspondence: Jonathan L. Curry ([jlcurry@mdanderson.org](jlcurry@mdanderson.org)) Received: 17 September 2025 | Revised: 8 December 2025 | Accepted: 5 January 2026 Keywords: bispecific antibodies | cutaneous adverse reactions | lichenoid dermatitis | lorigerlimab ABSTRACT Lorigerlimab is a dual bispecific antibody (BsAb) targeting cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein 1 that is used for treatment of advanced solid cancers such as metastatic castration-resistant prostate carcinoma. Reported cutaneous immune-related adverse events (irAEs) of lorigerlimab, such as pruritus and rash, are mostly manageable. However, to the best of our knowledge, the clinical histopathologic features of irAEs of the skin to dual immune checkpoint blockade with BsAbs have not been characterized. We report herein on lorigerlimab-associated lichenoid and vacuolar interface dermatitis in two patients with metastatic castration-resistant prostate adenocarcinoma. Case 1 had a violaceous, papular eruption and a lichenoid, perivascular histopathologic reaction pattern that responded well to temporary withholding of lorigerlimaband to corticosteroids. Case 2 presented with a more severe rash characterized by mixed clinical features of psoriasiform, eczematous, and morbilliform eruption and a histopathologic pattern of vacuolar interface changes with superficial perivascular lymphocytic infiltrate, scattered dyskeratotic keratinocytes, and focal acantholysis. The eruption was refractory to treatment, despite the patient withholding lorigerlimab, leading to complete discontinuation of lorigerlimab. This report highlights the importance of histopathologic evaluation in guiding treatment decisions for lorigerlimab-associated irAEs and underscores the need for further research into its dermatologic irAEs. 1 | Introduction Bispecific antibodies (BsAbs), which target two different antigens or epitopes, have become a part of treatment for hematologic malignancies and some advanced solid tumors. By recognizing two distinct antigens, they can recruit immune effector cells to attack tumor-specific targets. Based on their mechanisms of action, BsAbs can be classified into different groups, including bispecific T-cell engagers, immune checkpoint inhibitors (ICIs), and signaling pathway blockers [1] . BsAbs are reported to have relatively manageable side effects, if mild and include cytokine release syndrome and neurotoxicity; however, infrequently severe, life-threatening forms of these reactions that lead to organ dysfunction may occur and require intensive clinical monitoring and therapies [2, 3] . Tumor-infiltrating lymphocytes frequently co-express cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1), which is uncommon in peripheral T lymphocytes [4] . Lorigerlimab is a dual immune This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2026 The Author(s). Journal of Cutaneo

FAQs

What does lorigerlimab target and what cancer type is it used for?

Lorigerlimab is a dual bispecific antibody that targets CTLA-4 and PD-1 and is used for treatment of advanced solid cancers, including metastatic castration-resistant prostate carcinoma.

What skin toxicity patterns were reported in the two patients?

Both patients showed lorigerlimab-associated lichenoid and vacuolar interface dermatitis. Case 1 had a violaceous, papular lichenoid perivascular pattern, while Case 2 had more severe rash features with vacuolar interface changes and focal acantholysis.

How did treatment and discontinuation differ between the two cases?

Case 1 improved with temporary withholding of lorigerlimab and corticosteroids. Case 2 had refractory symptoms despite withholding, leading to complete discontinuation of lorigerlimab.

Sep 22, 2026

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