Immune Checkpoint Inhibitors in Transplantation—A Case Series and Comprehensive Review of Current Knowledge

Abstract

Cancer is a leading cause of morbidity and deaths in solid organ transplant recipients. In immunocompetent patients, cancer prognosis has been dramatically improved with the development of immune checkpoint inhibitors (ICI), as programmed cell death protein 1/programmed death-ligand 1 and cytotoxic T lymphocyte–associated antigen 4 inhibitors, that increase antitumor immune responses. ICI has been developed outside of the scope of transplantation because of the theoretical risk of graft rejection, which has later been confirmed by the publication of several cases and small series. The use of ICI became unavoidable for treating advanced cancers including in organ transplant patients, but their management in this setting remains highly challenging, as to date no strategy to adapt the immunosuppression and to prevent graft rejection has been defined. In this article, we report a monocentric series of 5 solid organ transplant recipients treated with ICI and provide a comprehensive review of current knowledge of ICI management in the setting of solid organ transplantation. Strategies warranted to increase knowledge through collecting more exhaustive data are also discussed.

Clinical outcomes of solid organ transplant recipients with metastatic cancers who are treated with immune checkpoint inhibitors: A single‐center analysis

“…5,6 To our knowledge, current data regarding the use of ICIs among SOTRs are limited to case reports, small case series, and case series reviews. [7][8][9][10] The goal of this study was to report our single-center experience of the safety, efficacy, and risks related to checkpoint inhibitor exposure in SOTRs.…”

Accelerated cellular rejection with prominent interstitial hemorrhage following cemiplimab treatment: How can we approach a renal transplant recipient under anti-PD1 therapy?

“…Data on the safety and efficacy of immune checkpoint inhibitors in kidney transplant patients were recently reviewed in a multicenter retrospective cohort 5 and systematic review. 6,7 Figure 1. Timeline of events since the day of transplantation to nephrectomy.…”

“…When calcineurin inhibitors are maintained in patients receiving anti PD-1, the majority preserves the graft, but with the cost of progression of the oncological disease since the T response amplification against the tumor cell is also avoided. 6,7 The combination of prednisone (5-10 mg daily) with mTOR inhibitors (mTORi) seems to have better results. We found six cases of patients who used mTORi with prednisone at the start of anti-PD-1 therapy have been reported, three of whom did not present rejection, and of these, two had good oncological response while one had progression of oncology disease.…”

“…10 Corticoids alone mostly led to graft rejection, with variable oncological response. [5][6][7] Once rejection was established, the majority of patients received high doses of bolus methylprednisolone, with responses depending on the severity of the rejection. We consider important to perform ultrasound follow-up of the graft since the magnitude of the inflammation can lead to complications that put the patient at risk of death Although allograft nephrectomies have been reported in the context of acute rejection, it is important to take into account in dialysis-dependent patients, the possibility of graft intolerance; we suggest minimizing but not total immunosuppression withdrawing.…”

Der Einsatz der immunonkologischen Therapie beim hepatozellulären Karzinom im Kontext der Lebertransplantation Eine interdisziplinäre Risiko-Nutzen-Abwägung

“…Eine Abstoßung scheint bei 30-40 % der Patienten aufzutreten (▶ Tab. 1;[7,8,9,10,11,12,13,14,15,16,17,18,19,20]). Allerdings werden auch Fälle berichtet, bei denen keine Abstoßung auftrat und Tumoransprechen beobachtet wurde.…”