{
  "abstract": "Background In the C-144-01 phase II trial of lifileucel – a first-in-class autologous tumor-infiltrating lymphocyte (TIL) therapy recently approved for advanced/metastatic melanoma – and up to six interleukin-2 (IL-2) doses, 1 2 ‘rash’ was a treatment-emergent adverse event in 37.2% of individuals 3 TIL/IL-2-associated eruptions have not yet been described or associated with tumor response.Methods The MGB/DFCI Research Patient Data Registry was queried for patients who received ‘lifileucel,’ ‘Amtagvi,’ or ‘LN-144.’ The lifileucel admission and oncology follow-up encounters were reviewed for demographics, eruption features, dermatopathology, and oncologist assessments of tumor response on 30-day post-TIL restaging scans. 4 A pre-specified crude sensitivity analysis tested for independent association between IL-2 dosing (‘high IL-2’ as 4-6 doses; ‘low IL-2’ as 1-3 doses), rash, and 30-day response. Binomial family linear regressions modeled tumor response as a binary outcome, with development of lifileucel/IL-2 skin toxicity as a binary predictor. Adjustments were made for age, sex, IL-2 dose number, and TIL delivery-to-discharge days.Results Among 44 individuals (34.1% female; median age 57 years), 22 (50.0%) developed a lifileucel-associated cutaneous eruption ( table 1). Eruptions were asymptomatic or mildly pruritic central-predominant morbilliform eruptions with occasional purpuric features (figure 1A-F). Dermatopathology from a representative case demonstrated a lymphocyte-predominant interface infiltrate with rare eosinophils and dermal mucin (figure 1G-J).Individuals with cutaneous eruptions had a significantly higher 30-day ORR than those who did not develop cutaneous eruptions (68.2% vs 27.3%, p=0.01). Female sex also was descriptively associated with an increased ORR (80.0% vs 31.0%, Fisher’s p=0.004). Individuals who developed skin toxicity received more mean IL-2 doses (4.77 vs 3.64, p=0.02); however, ‘high IL-2’ recipients did not more frequently demonstrate response (high IL-2: 50.0% vs low IL-2: 43.8%, p=0.76).In the unadjusted logistic regression, lifileucel/IL-2 skin toxicity was associated with tumor response (OR 5.71, 95%CI 1.63–22.47, p=0.009). This association was durable when adjusted for IL-2 dose number (aOR 7.21, 95%CI 1.81–36.28, p=0.008), and when adjusted for age, sex, TIL delivery-to-discharge days, and IL-2 dose number (a’OR 11.59, 95%CI 2.06–100.59, p=0.011).Conclusions This study demonstrates a positive prognostic association between lifileucel-associated morbilliform eruptions and 30-day ORR. While IL-2 monotherapy can cause similar morbilliform eruptions, 5 6 this IL-2-dose-adjusted analysis suggests that lifileucel-associated skin toxicity may represent a non-IL-2-mediated marker of underlying anti-tumor efficacy, assessable during the lifileucel-associated hospital admission 3-4 weeks prior to 30-day restaging. Limitations include sample size, retrospective data, and selection bias favoring more pronounced cutaneous eruptions; we recommend future analyses investigating further-out response endpoints.References Chesney J, Lewis KD, Kluger H, et al. Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study. J Immunother Cancer. 2022;10(12):e005755. doi:10.1136/jitc-2022-005755Thomas SS, Gogas H, Hong YK, et al. Efficacy and safety of lifileucel, an autologous tumor-infiltrating lymphocyte cell therapy, and pembrolizumab in patients with immune checkpoint inhibitor-naive unresectable or metastatic melanoma: Updated results from IOV-COM-202 cohort 1A. J Clin Oncol. 2024;42(16_suppl):9505-9505. doi:10.1200/JCO.2024.42.16_suppl.9505Food and Drug Administration. AMTAGVI (lifileucel) suspension for intravenous infusion: package insert. Published online 2024. https://www.fda.gov/media/176417/download?attachmentSchwartz LH, Litière S, de Vries E, et al. RECIST 1.1-Update and clarification: from the RECIST committee. Eur J Cancer Oxf Engl. 1990. 2016;62:132-137. doi:10.1016/j.ejca.2016.03.081Wolkenstein P, Chosidow O, Wechsler J, et al. Cutaneous side effects associated with interleukin 2 administration for metastatic melanoma. J Am Acad Dermatol. 1993;28(1):66-70. doi:10.1016/0190-9622(93)70011-hLudwig C, Goh V, Rajkumar J, Au J, Tsoukas M. Drug eruptions associated with tumor therapy: Great imitators. Clin Dermatol. 2020;38(2):208-215. doi:10.1016/j.clindermatol.2019.10.006Ethics Approval This study was approved by the Mass General Brigham IRB, under Protocol #: 2020P002307.Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.Abstract 380 Table 1Patient characteristics a Pembrolizumab (2); b Encorafenib/binemetenib (1); Dabrafenib/trametinib (1); Ripretinib (1); All p-values are calculated from Fisher’s exact test, except for two-tailed t-tests where indicated (*) to compare independent means, with alpha set at 0.05Abstract 380 Figure 1Clinical photography and dermatopathology of lifileucel/interleukin-2-associated morbilliform eruption. A) Face. B) Chest. C) Back. D, E) Bilateral arms; left arm biopsy site. F) Bilateral legs. G-H) Interface dermatitis (H&E stain, 200x and 400x). I) Rare eosinophils (circled) (H&E stain, 600x). J) Colloidal iron stain with dermal mucin (400x)",
  "authors": [
    {
      "affiliations": [
        "Harvard Medical School, Boston, MA, USA",
        "Brigham and Women’s Hospital, Boston, MA, USA",
        "Massachusetts General Hospital, Boston, MA, USA"
      ],
      "name": "Jordan T Said"
    },
    {
      "affiliations": [
        "Harvard Medical School, Boston, MA, USA",
        "Brigham and Women’s Hospital, Boston, MA, USA",
        "Massachusetts General Hospital, Boston, MA, USA"
      ],
      "name": "Nakisa Sadeghi"
    },
    {
      "affiliations": [
        "Massachusetts General Hospital, Boston, MA, USA"
      ],
      "name": "Yunxi Li"
    },
    {
      "affiliations": [
        "Harvard Medical School, Boston, MA, USA",
        "Mass General Cancer Center, Boston, MA, USA"
      ],
      "name": "Ryan J Sullivan"
    },
    {
      "affiliations": [
        "Harvard Medical School, Boston, MA, USA",
        "Mass General Cancer Center, Boston, MA, USA"
      ],
      "name": "Donald Lawrence"
    },
    {
      "affiliations": [
        "Harvard Medical School, Boston, MA, USA",
        "Brigham and Women’s Hospital, Boston, MA, USA",
        "Massachusetts General Hospital, Boston, MA, USA",
        "Mass General Cancer Center, Boston, MA, USA",
        "Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA",
        "Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA",
        "Dana-Farber Cancer Institute, Boston, MA, USA",
        "Harvard University, Cambridge, MA, USA"
      ],
      "name": "Alexandra Haugh"
    },
    {
      "affiliations": [
        "Harvard Medical School, Boston, MA, USA",
        "Massachusetts General Hospital, Boston, MA, USA",
        "Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA"
      ],
      "name": "Genevieve M Boland"
    },
    {
      "affiliations": [
        "Massachusetts General Hospital, Boston, MA, USA",
        "Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA",
        "Dana-Farber Cancer Institute, Boston, MA, USA"
      ],
      "name": "Sonia Cohen"
    },
    {
      "affiliations": [
        "Harvard Medical School, Boston, MA, USA",
        "Harvard University, Cambridge, MA, USA"
      ],
      "name": "Elizabeth I Buchbinder"
    },
    {
      "affiliations": [
        "Harvard Medical School, Boston, MA, USA",
        "Harvard University, Cambridge, MA, USA"
      ],
      "name": "David Liu"
    },
    {
      "affiliations": [
        "Harvard Medical School, Boston, MA, USA",
        "Massachusetts General Hospital, Boston, MA, USA"
      ],
      "name": "Kristine M Cornejo"
    },
    {
      "affiliations": [
        "Harvard Medical School, Boston, MA, USA",
        "Brigham and Women’s Hospital, Boston, MA, USA",
        "Harvard University, Cambridge, MA, USA"
      ],
      "name": "Nicole R LeBoeuf"
    },
    {
      "affiliations": [
        "Harvard Medical School, Boston, MA, USA",
        "Massachusetts General Hospital, Boston, MA, USA"
      ],
      "name": "Yevgeniy R Semenov"
    }
  ],
  "title": "380 Cutaneous eruptions associated with lifileucel, a first-in-class tumor-infiltrating lymphocyte therapy, and interleukin-2 in individuals with metastatic melanoma: a retrospective prognostic analysis",
  "uid": "764f8268-32d1-50b3-a591-0c193988a68f"
}