Exceptional Response of Cryoablation Followed by Pembrolizumab in a Patient with Metastatic Cervical Carcinosarcoma with High Tumor Mutational Burden: A Case Report.

Cervical carcinosarcoma is an extremely rare type of neoplasm that lacks standard of care. Preclinical and clinical evidence has suggested that cryoablation in combination with immunotherapy may result in a synergistic effect, generating a more robust immune response to distant lesions. A few clinical trials have evaluated the efficacy of such combination treatment in a variety of solid tumors, but with conflicting results. This report describes the first clinical efficacy of cryoablation followed by pembrolizumab observed in a patient with tumor mutational burden (TMB)-high metastatic cervical carcinosarcoma that was negative for programmed cell death protein 1 expression, microsatellite instability stable, and had mutations in DNA polymerase epsilon (POLE). She had achieved complete response (CR) after 3 months of pembrolizumab treatment and had maintained CR as of the time of submission of this manuscript, with a progression-free survival of 11 months and counting. The case exhibited an exceptional response to cryoablation followed by pembrolizumab, potentially attributed to mutations in POLE, which lead to an extremely high TMB. This report paves the avenue for establishing treatment regimens for patients with TMB-high cervical carcinosarcoma. KEY POINTS: Owing to its rarity, cervical carcinosarcoma has not been well characterized, and currently, there is no standard of care for this disease. This report describes the first case of clinical efficacy of cryoablation followed by pembrolizumab observed in a patient with tumor mutational burden-high metastatic cervical carcinosarcoma. The case exhibited an exceptional response (maintained CR as of the time of submission of this article: 11 months) to cryoablation followed by pembrolizumab. This is the first POLE-mutated cervical carcinosarcoma case.