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IMPORTANCE: Lifileucel is a first-in-class autologous tumor-infiltrating lymphocyte (TIL) therapy for advanced/metastatic melanoma with progression after anti-programmed cell death protein 1 (PD-1) therapy and/or BRAF inhibitor therapy, if BRAF V600 mutations are present. In the C-144-01 phase 2 trial of lymphodepleting chemotherapy, lifileucel, and interleukin 2 (IL-2), cutaneous eruption occurred in 37.2% of individuals. These eruptions remain clinically and prognostically unknown.OBJECTIVE: To examine cutaneous toxic effects development in the setting of lifileucel therapy, abstract clinical and histopathologic eruption features, and test for association with objective radiographic tumor response.DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was performed at Mass General Brigham (MGB)/Dana-Farber Cancer Institute (DFCI) that included all patients treated with lifileucel, outside of active clinical trials. The analysis was completed in December 2025.EXPOSURES: All individuals received cyclophosphamide/fludarabine lymphodepletion, lifileucel, and 6 or fewer IL-2 infusions. Demographics, melanoma-specific factors (M stage, pre-TIL lactate dehydrogenase levels, and number of lines of prior systemic therapy), number of IL-2 doses received, eruption features, photography, and dermatopathologic findings were abstracted.MAIN OUTCOMES AND MEASURES: Radiographic responses 30 to 41 days, 42 to 89 days, and 90 days or longer from TIL infusion per Response Evaluation Criteria in Solid Tumors (RECIST) were abstracted. Individuals were stratified as high IL-2 (4-6 doses) or low IL-2 (1-3 doses), for objective response rate (ORR) comparison as a descriptive sensitivity analysis. An unadjusted logistic regression modeled tumor response as a binary outcome with lifileucel-associated eruption occurrence as a binary predictor. Three adjusted models included IL-2 doses (age, sex, and demographic differences) and melanoma-specific factors as covariates.RESULTS: Per retrospective electronic medical health record review, among 44 individuals (34.1% female individuals; mean [SD] age, 54.8 [14.5] years), treated with lifileucel (median, 4.5 IL-2 doses), 22 (50.0%) developed an associated cutaneous eruption while hospitalized, after a median of 4 post-TIL days. Photographs from 14 of 22 individuals (63.6%) with available images demonstrated central-predominant, frequently purpuric morbilliform eruptions. ORRs did not significantly differ by IL-2 stratification (high IL-2: 50.0% vs low IL-2: 37.5%; P = .53). Cutaneous eruption development was associated with a 42-day response across analyses (analysis 1: OR, 7.29; 95% CI, 1.91-27.86; P = .004; OR, 7.65; 95% CI, 1.79-32.69; P = .006; analysis 2: OR, 11.95; 95% CI, 1.90-75.39; P = .008; analysis 3: OR, 9.73; 95% CI, 2.12-44.74; P = .003); 30-day responses were statistically similarly associated. All 90-day cutaneous eruption response analyses did not detect statistical significance.CONCLUSIONS AND RELEVANCE: In this cohort study, lifileucel treatment was frequently complicated by purpuric morbilliform eruptions, which were prognostically favorable and associated with short-term response. The lifileucel-associated eruption may be a peritreatment efficacy marker, assessable during the TIL treatment hospitalization prior to traditional 42-day restaging.