Successful administration of sequential TVEC and pembrolizumab followed by Temozolomide in immunotherapy refractory intracranial metastatic melanoma with acquired B2M mutation

Despite the substantial advances in the management of metastatic melanoma with the introduction of immune checkpoint inhibitors (ICI), many patients develop disease progression during treatment with immunotherapy. This has been suggested to be mediated by several mechanisms that contribute to acquired resistance to ICI, one of which is acquired beta-2 microgloubulin (B2M) mutation. Talimogene laherparepvec (TVEC) is a genetically modified oncolytic virus that can enhance antitumor immunity. Temozolomide (TMZ) is an oral alkylating agent that has been suggested to augment anti-tumor immune response. The clinical significance of TVEC and TMZ in metastatic melanoma patients who are refractory to immunotherapy is unknown. We report a case of a patient with immunotherapy refractory intracranial metastatic melanoma after initial response to ICI who had acquired B2M mutation. The patient received TVEC and pembrolizumab followed by TMZ. The patient maintained durable response of her visceral and intracranial disease for 19 months and ongoing. More research is essential to delineate whether TVEC or TMZ has efficacy in immunotherapy refractory metastatic melanoma with acquired B2M mutation.