The diverse landscape of dermatologic toxicities of non‐immune checkpoint inhibitor monoclonal antibody‐based cancer therapy

Abstract

Background Since their first approval 25 years ago, monoclonal antibodies (mAbs) have become important targeted cancer therapeutics. However, dermatologic toxicities associated with non−immune checkpoint inhibitor (non‐ICI) mAbs may complicate the course of cancer treatment. Data on the incidence and types of these reactions are limited. Methods A comprehensive review was conducted on dermatologic toxicities associated with different classes of non‐ICI mAbs approved for treatment of solid tumors and hematologic malignancies. The review included prospective Phase 1, 2, and 3 clinical trials; retrospective literature reviews; systematic reviews/meta‐analyses; and case series/reports. Results Dermatologic toxicities were associated with several types of non‐ICI mAbs. Inflammatory reactions were the most common dermatologic toxicities, manifesting as maculopapular, urticarial, papulopustular/acneiform, and lichenoid/interface cutaneous adverse events (cAEs) with non‐ICI mAbs. Immunobullous reactions were rare and a subset of non‐ICI mAbs were associated with the development of vitiligo cAEs. Conclusion Dermatologic toxicities of non‐ICI mAbs are diverse and mostly limited to inflammatory reactions. Awareness of the spectrum of the histopathologic patterns of cAE from non‐ICI mAbs therapy is critical in the era of oncodermatology and oncodermatopathology.

Inflammation of actinic keratosis from chemotherapy in a relapsed multiple myeloma patient

“…Although the inflammation of AK from immune checkpoint inhibitors has not been specifically reported, they can potentially lead to such manifestations through diversification of T-lymphocyte and B-lymphocyte populations and subsequent skin damage mediated by inflammatory cytokines and autoantibodies 11. Non-immune checkpoint inhibitor monoclonal antibody-based cancer therapies can also lead to inflamed AK by coexpression of their targets on keratinocytes 12. The dysregulation of the epidermal growth factor receptor and vascular endothelial growth factor receptor pathway in AK may explain the inflammation from panitumumab, erlotinib and sorafenib 13–16.…”

Gene expression profiling and multiplex immunofluorescence analysis of bullous pemphigoid immune‐related adverse event reveal upregulation of toll‐like receptor 4/complement‐induced innate immune response and increased density of TH1 T‐cells

“…1 They occur in fewer than 1% of patients treated with targeted inhibitors of BRAF and other small-molecular inhibitors. 1,2 Bullous pemphigoid (BP)-irAE is the most commonly reported autoimmune blistering process among cancer patients treated with anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapies. 3,4 A review of 58 cases of BP-irAE associated with anti-PD-1/PD-L1 immunotherapy demonstrated a median latency of $28 weeks and most often clinical presentation as an eczematous or urticarial lesion or blisters (80%) with a histopathologic pattern of subepidermal bullae (71%) and eosinophils (81%).…”

“…Immunobullous skin eruptions constitute a small but significant proportion of immune‐related adverse events (irAEs) to anticancer therapies 1 . They occur in fewer than 1% of patients treated with targeted inhibitors of BRAF and other small‐molecular inhibitors 1,2 . Bullous pemphigoid (BP)‐irAE is the most commonly reported autoimmune blistering process among cancer patients treated with anti‐programmed cell death protein 1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) and anti‐cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) therapies 3,4 .…”