{
  "abstract": "Background Tebentafusp is a bispecific antibody used to treat metastatic uveal melanoma patients through targeting the HLA-A*02:01 antigen. Cutaneous adverse events (cAEs) have been observed to occur in up to 83% of patients on tebentafusp. 1 However, data is limited on the extent to which toxicity and its severity impacts patient survival.2–4 Methods To investigate the prognostic implications of tebentafusp-associated cAEs, we conducted a multi-center retrospective cohort analysis of HLA-A*02:01-positive metastatic uveal melanoma patients seen at tertiary care institutions from Ludwig Maximilian University Munich and Mass General Brigham and Dana Farber Cancer Institute between January 1st, 2018, to May 31st, 2025. cAEs were identified as ≥1 erythematous patch associated to the first three administrations of tebentafusp and stratified by severity using common terminology criteria for adverse events (CTCAE) grading. 5 We evaluated best tumor response using RECIST criteria6 and progression after tebentafusp initiation. Cox regression analyses were conducted at a landmark time of 1 month after tebentafusp was started to analyze the prognostic impact of the presence and severity of cAEs on overall survival (OS).Results A total of 83 patients were identified. cAEs were observed in 78.3% (n=65) of patients with 50.8% (n=33) CTCAE Grade 1 and 49.2% (n=32) CTCAE Grade ≥2. Of these 65 patients, 60 (90.7%) experienced a cAE within 1 month of tebentafusp initiation. Progression after tebentafusp initiation was observed in 86.7% (n=72) of treated patients. RECIST best tumor response consisted of 12.0% (n=10) partial response, 43.4% (n=36) stable disease, and 44.6% (n=37) progressive disease ( table 1). Patients who experienced skin toxicity exhibited a significantly longer OS versus those without cAEs in both univariate (median 23.0 months versus 7.5 months, p=2.65e-05) and multivariate Cox regression analyses (hazard ratio (HR) [95% CI] = 0.27 [0.12, 0.63], p=0.002). Furthermore, OS benefit was accentuated in patients with Grade 2 or above (0.22 [0.09, 0.54] p=0.001) and Grade 1 (0.35 [0.14, 0.85], p=0.02) cAEs versus patients without cAEs (table 2).Conclusions In this multi-institutional study, we found that cAEs from tebentafusp therapy were associated with significantly increased overall survival in uveal melanoma patients, with more pronounced prognostic benefits seen in those with higher grade cAEs. These results suggest that tebentafusp-associated cAEs may serve as an early clinical marker of therapeutic efficacy. Future studies are warranted to elucidate the underlying mechanisms driving this relationship.References Nathan P, Hassel JC, Rutkowski P, et al. Overall survival benefit with tebentafusp in metastatic uveal melanoma. N Engl J Med. 2021;385(13):1196–1206.Tomsitz D, Kerl K, French LE, Heinzerling L. Clinical and pathological characterization of tebentafusp-associated skin toxicity: a cohort study with 33 patients. J Am Acad Dermatol. 2024;91(6):1136-1142.Riew GJ, Hijaz BA, Haq R, et al. Severity and progression of dermatologic adverse events associated with tebentafusp: a retrospective multicenter cohort study. J Am Acad Dermatol. Published online 2025 Jun 12.Tomsitz D, Ruf T, Heppt M, et al. Tebentafusp in patients with metastatic uveal melanoma: a real-life retrospective multicenter study. Cancers (Basel). 2023;15(13):3430.Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, National Institutes of Health [https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf]Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45(2):228–47.Ethics Approval The study was approved by the Mass General Brigham Institutional Review Board (Protocol #2022P002518).Consent The study meets the criteria of secondary research, for which patient consent was not required.Abstract 1039 Table 1Baseline characteristics of metastatic uveal melanoma patients treated with tebentafusp acAE = cutaneous adverse event; bcAEs were stratified by severity using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grading; cBest tumor response following tebentafusp initiation was evaluated using RECIST version 1.1; PD – progressive disease; PR – partial response; SD – stable disease.Abstract 1039 Table 2Overall survival among metastatic uveal melanoma patients treated with tebentafusp acAE = cutaneous adverse event; bCI = confidence interval; ccAEs were stratified by severity using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0",
  "authors": [
    {
      "affiliations": [
        "University Hospital LMU, LMU Munich, Munich, Germany"
      ],
      "name": "Lisa Arnold"
    },
    {
      "affiliations": [
        "Massachusetts General Hospital, Boston, MA, USA"
      ],
      "name": "Christopher J Thang"
    },
    {
      "affiliations": [
        "Massachusetts General Hospital, Boston, MA, USA"
      ],
      "name": "Yunxi Li"
    },
    {
      "affiliations": [
        "University Hospital LMU, LMU Munich, Munich, Germany"
      ],
      "name": "Friedrich Caroli"
    },
    {
      "affiliations": [
        "Massachusetts General Hospital, Boston, MA, USA"
      ],
      "name": "Charles Lu"
    },
    {
      "affiliations": [
        "Massachusetts General Hospital, Boston, MA, USA"
      ],
      "name": "Olivia Burke"
    },
    {
      "affiliations": [
        "University Hospital LMU, LMU Munich, Munich, Germany"
      ],
      "name": "Monika Morak"
    },
    {
      "affiliations": [
        "University Hospital LMU, LMU Munich, Munich, Germany"
      ],
      "name": "Dirk Tomsitz"
    },
    {
      "affiliations": [
        "Massachusetts General Hospital, Boston, MA, USA"
      ],
      "name": "Yevgeniy R Semenov"
    },
    {
      "affiliations": [
        "University Hospital LMU, LMU Munich, Munich, Germany",
        "Uniklinikum Erlangen, Deutsches Zentrum Immuntherapie, Comprehensive Cancer Center Erlangen – EMN, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany"
      ],
      "name": "Lucie Heinzerling"
    }
  ],
  "title": "1039 Evaluating the prognostic impact of tebentafusp-associated cutaneous toxicities on survival in 83 uveal melanoma patients: a multi-institutional cohort study",
  "uid": "05a9456b-b937-5740-b984-6ec3097ff7f7"
}