Successful administration of sequential TVEC and pembrolizumab followed by Temozolomide in immunotherapy refractory intracranial metastatic melanoma with acquired B2M mutation
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Karam Khaddour1, Joshua Dowling2, Jiayi Huang3, Martha Council4, David Chen4, Lynn Cornelius4, Tanner Johanns1, Sonika Dahiya5 and George Ansstas1
1 Department of Medicine, Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri, USA
2 Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
3 Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA
4 Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri, USA
5 Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA
Keywords: metastatic melanoma; immune checkpoint inhibitor; temozolomide; acquired resistance; beta-2 microglobulin
Received: August 31, 2020 Accepted: December 08, 2020 Published: December 29, 2020
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.
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