Biopsied Cutaneous Adverse Effects of PD-1 and PD-L1 Checkpoint Inhibitors and Progression-free Survival: A Retrospective Case Series of 75 Patients

ABSTRACT: Programmed cell death-1 checkpoint inhibitors have significantly improved cancer survival outcomes. More than half of patients on programmed cell death-1 checkpoint inhibitors develop cutaneous immune-related complications. The prognostic significance of eruptions biopsied in routine clinical practice remains underexplored. We aimed to characterize biopsy-confirmed cutaneous toxicities associated with checkpoint inhibitors and assess their association with survival. We conducted a retrospective study of biopsy-confirmed checkpoint inhibitor-associated dermatoses at our single institution between September 2014 and June 2025, analyzing clinical features, histopathology, treatment outcomes, and progression-free (PFS) and overall survival. Seventy-five patients were included (mean age 67.0 years [24, 95]; 52% female). Most developed reactions within 6 months of initiating therapy. Most took pembrolizumab and nivolumab. Histopathologic categories included type IV hypersensitivity (T4HS) lichenoid (N = 29; 39%), T4HS eczematoid (N = 10; 13%), other T4HS patterns (N = 6; 8%) including 1 fatal case of toxic epidermal necrolysis, vesiculobullous (N = 12; 16%), psoriasis (N = 4; 5%), reversible epitheliotropic T-cell dyscrasia (N = 4; 5%), sclerodermoid (N = 4; 5%), Sweet syndrome (N = 3; 4%), and miscellaneous (N = 3; 4%). Most eruptions improved or remained stable with treatment with 1 fatal case of toxic epidermal necrolysis. Patients with T4HS-mediated reaction, 60% of our cohort, had reduced tumor progression hazard with longer PFS (hazard ratio = 0.49 [0.23-1.05], P = 0.07; PFS-padj = 0.06, PFS-late-weighted padj = 0.04). Overall survival did not differ. Our study is limited by sample size. Checkpoint inhibitor-associated dermatoses resemble established standard cutaneous adaptive B- and T-cell-driven dermatoses. Regulatory T-cell inhibition, allowing emergence of autoreactive B and T cells or unmasking of subclinical hypersensitivity, is likely pathogenetically key.