Immunotherapy for Gestational Trophoblastic Neoplasia: A New Paradigm

Background: Immune checkpoint immunotherapy (CPI) targeting programmed cell death 1 (PD-1)/ligand (PD-L1) has been shown to be an effective treatment for gestational trophoblastic neoplasia (GTN). This includes those with multidrug resistance, ultra-high-risk disease, and epithelioid trophoblastic tumour/placental site trophoblastic tumour subtypes that are inherently chemotherapy resistant, but there is also emerging evidence in low-risk disease.

Objectives: We set out to generate an overview of the current data supporting the use of CPI for GTN in both high-risk and low-risk disease and to consider future research goals and directions in order to implement CPI in current treatment guidelines.

Methods: We identified and reviewed the published data on the use of CPI agents in GTN.

Outcome: 133 patients were identified who had been treated with CPI for GTN with pembrolizumab (23), avelumab (22), camrelizumab (57), toripalimab (15), or other anti-PD-1 agents (16), of whom 118 had high-risk diseases, relapse or multi-drug resistant disease, and 15 low-risk diseases. Overall 85 patients achieved complete remission, 77 (of 118) with high-risk disease, and 8 (of 15) with low-risk disease. 1 patient with complete remission in the high-risk group developed a relapse 22 months after anti-PD-1 treatment had been stopped. Treatment was generally well tolerated across studies.

Conclusions and outlook: The majority of high-risk patients (77/118) treated with CPI are cured and this is particularly relevant amongst those with chemotherapy resistant disease who otherwise have very limited treatment options. Priorities for future research include determining whether these agents have a role earlier in the disease course, the utility of combination with chemotherapy, and effects on future fertility. Treatment availability remains a concern due to the high price of these agents.