Tebentafusp desensitization in an adult with metastatic uveal melanoma

IntroductionMetastasis occurs in almost 50% of patients with uveal melanoma. In patients who are HLA-A*02:01 positive, first line treatment is the Immune mobilizing monoclonal T cell receptor Against Cancer (ImmTAC), tebentafusp, which increases overall survival significantly at one year compared to single-agent immunotherapy or chemotherapy. Hypersensitivity reactions (HSR) to cancer therapeutics are well established. When these therapies offer significant benefits over alternatives, drug desensitization protocols are utilized to improve clinical outcomes in those with suspected IgE-mediated HSRs.Case reportWe present a case of an individual with metastatic uveal melanoma who suffered an anaphylactic HSR to tebentafusp. Given the lack of available ImmTAC therapeutic desensitization protocols, this report's purpose was to create a tebentafusp desensitization protocol based on accepted desensitization protocols for other chemotherapeutic drugs.Management and outcomeThe desensitization procedure consisted of pretreatment with cetirizine, famotidine, diphenhydramine, methylprednisolone, and acetaminophen prior to infusion. Infusions were each given as two diluted infusions limited to 100 mL of reconstitution volume, with cumulative quantities equivalent to standard treatment regimen dosages. Drug was given over no longer than four hours per manufacturer's recommendations. A total of three cycles of three weekly infusions were completed. The patient had no anaphylaxis recurrence. Tebentafusp treatment was withheld after the third cycle due to disease progression.DiscussionFor patients with HLA-A*02:01 positive metastatic uveal melanoma with suspected IgE-mediated HSR to tebentafusp, desensitization can be completed safely. Given the patient's disease progression within two months of treatment, it is unknown whether desensitization impacts the drug's clinical benefit.