DO NOT USE IMMUNOTHERAPY IN TRANSPLANT PATIENTS

Efficacy and Tolerance of Immune Checkpoint Inhibitors in Transplant Patients With Cancer

A Systematic Review

Thibaut d'Izarny-Gargas; Antoine Durrbach; Mohamad Zaidan

American Journal of Transplantation. 2020;20(9):2457-2465. 

Abstract and Introduction

Abstract

Solid organ transplant (SOT) is frequently complicated by cancers, which render immunosuppression challenging. Immune checkpoint inhibitors have emerged as treatments for many cancers. Data are lacking regarding efficacy and rejection risk in the SOT population. We conducted a systematic literature review and analyzed 83 cases of immune checkpoint inhibitor use for cancer in SOT. Two thirds of these patients received anti–programmed death ligand 1 therapy, 15.7% received anti–cytotoxic T lymphocyte–associated protein 4 therapy, and 10.8% received a combination. Allograft rejection occurred in 39.8% of patients, leading to end-stage organ failure in 71.0% of cases. Outcomes were similar across organs and immunotherapy regimens. The use of immunosuppressants other than steroids, time since transplant, and prior episodes of rejection were associated with the risk of rejection. The median overall survival of patients was 36 weeks. Most of the deaths were related to cancer progression. In nonkidney recipients, graft rejection was strongly associated with worse survival. At the end of the study, 19.3% of the patients were alive, free from rejection and tumor progression. This study highlights the difficult tradeoff facing oncologists and transplant specialists managing transplant recipients with cancer, and the need for prospective data and novel biomarkers for identifying the patients likely to benefit from immunotherapy in the SOT setting.

Conclusion

In summary, the use of CPIs in the field of oncology has paved the way for new perspectives for the treatment of patients suffering from cancers, including SOTRs. Unfortunately, even though one-third of transplant patients respond positively to treatment in terms of cancer outcome, the antitumor efficacy of CPIs appears to be too low to outweigh the high and unpredictable risk of severe organ rejection, potentially leading to death.

Clinicians wishing to initiate immunotherapy in SOTRs with cancer should consider the type of organ transplanted, the prognosis of the cancer, and the expected response rate. Changes in the management of immunosuppression should be considered at expert centers and evaluated on a case-by-case basis. Obtaining the consent of patients informed about the risks and benefits of treatment is of the utmost importance. Direct collaboration between organ transplant specialists and oncologists, and the validation of predictive biomarkers, will be required to overcome the issues outlined by this review.