Advanced cancers treated with PD-L1 inhibitors and CTLA-4 antagonist in transplanted immunosuppressed patients: systematic review of graft outcome
Giuseppe Ietto1, Marika Morabito1, Marta Ripamonti1, Martina Pardo1, Elia Zani1, Domenico Iovino1, Cristiano Parise1, Giulio Carcano1.
1General, Emergency and Transplant Surgery Department, ASST-Settelaghi and University of Insubria, Varese, Italy
Background: Cancer is a major cause of morbidity and mortality in transplanted patients: its overall risk is increased two to three times compared to the general population, and it’s inversely related to age, with younger recipients experiencing a greater relative increase in risk compared to older recipients. Plus, the prognosis is worse for recipients diagnosed with cancer, compared to the general population, because of immunosuppressive drugs. The aim of this study is to demonstrate a correlation between use of CTLA-4 antagonist and PD-L1 inhibitors in transplanted patients with de novo malignancies and grafts outcome.
Methods: A literature review concerning the use of anti PD-L1 and CTLA-4 antagonists in transplanted patients with advanced neoplasm was performed. The analyzed variables were: age, sex, transplanted solid organ, immunosuppressive induction and maintenance therapy performed, type of cancer developed, developmental latency time, anticancer drugs administered, possible rejection and related therapy administered, patient outcome.
Results: A sample of 52 patients was sort from the literature review. The statistical analysis revealed that no variables had a significant correlation with graft rejection after the use of checkpoint inhibitors. The use of CTLA-4 antagonists seems to be associated with a less significant risk of development of graft rejection than PD-L1 inhibitors (OR = 4.00, p = 0.06).
Conclusions: The available data suggest that CTLA-4 antagonists are safer in transplanted patients than PD-L1 inhibitors, which were associated with a higher risk of allograft rejection. This study didn’t identify an agent responsible for different outcomes between patients treated with PD-L1 inhibitors and CTLA-4 antagonists. Checkpoint inhibitors have proved to be valid for treatment of various malignancies, but transplanted cancer patients have never been included in clinical trials on their efficacy, because of the risk of graft rejection. Further studies and trials are needed to ensure these patients the best possible treatments.
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