Cutaneous adverse events following CAR T-cell therapy in hematologic malignancies

Chimeric antigen receptor (CAR) T-cell therapy has transformed outcomes for patients with relapsed or refractory (R/R) hematologic malignancies [1], particularly diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and B-acute lymphoblastic leukemia (B-ALL).While cytokine release syndrome and neurotoxicity are well-characterized toxicities of CAR T-cell therapy, data on associated cutaneous adverse events (AEs) are limited [2-4].Hence, we sought to evaluate the incidence, type, and timing of cutaneous AEs following CAR T-cell therapy.This is a single center retrospective cohort study of patients with of R/R B-cell lymphoma, B-ALL, or multiple myeloma who were treated with commercial CAR-T products (axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel, brexucabtagene autoleucel, or idecabtagene vicleucel) between January 1, 2016, and September 1, 2022, at Ohio State University.Medical records were reviewed to determine the incidence and severity of cutaneous AEs following CAR T-cell therapy.Treating oncologist documentation, dermatology consultation notes, and skin biopsy findings were systematically assessed.Two authors (C.P. and W.P.) independently adjudicated each cutaneous AE and classified its likelihood of association with CAR T-cell therapy as low or high.High likelihood of association was defined as lack of alternative etiologies for cutaneous AE.Cases with uncertain attribution were reviewed by a third author (E.U.) to reach consensus.Only cutaneous AEs deemed to have a high likelihood of association with CAR T-cell therapy were included in the analysis.Cutaneous AEs were graded per CTCAE v5.0.Cutaneous AEs were categorized based on the time of onset following CAR-T infusion as early-onset (within 30 days), intermediate-onset (31-180 days), and late-onset (beyond 180 days).The study was approved by the institutional review board at Ohio State University and was conducted in compliance with the Declaration of Helsinki.As this was a retrospective study, informed consent was waived.Among the 246 patients included in the study, 97% (n = 228) were treated for R/R B-cell lymphomas and B-ALL, and 3% (n = 18) for R/R multiple myeloma.Median follow-up was 576 days (range 16 -2041 days).Among these, cutaneous AEs of high likelihood of association with CAR T-cell therapy occurred in 23 patients and were the population of interest.An additional 34 patients had cutaneous AEs deemed to be of low likelihood of association with CAR T-cell therapy.Table 1 outlines the characteristics of patients with cutaneous AEs following CAR T-cell therapy.The median age was 66 years (range 54-78), with 65% males.The median number of lines of therapy prior to CAR-T was 3 (range, 2-7).Five (22%) patients