Immune checkpoint inhibitors in kidney transplantation

Abstract

Purpose of review The development of immune checkpoint inhibitor (ICI) immunotherapy has revolutionized the treatment of several cancers. Malignancies are one of the leading causes of death in solid organ transplant recipients (SOTRs). Although ICI treatment may be an effective option in treating malignancies in SOTRs, concerns about triggering allograft rejection have been raised in this population. Herein, we will review currently available data regarding patients, allograft and malignancy outcomes in SOTRs who received ICI therapy. Recent findings Cancer incidence is three to five-fold higher among SOTRs, compared with the general population. Skin cancer is the most prevalent cancer after transplant, followed by kidney cancer, lymphoma and Kaposi sarcoma. There are no large prospective studies evaluating ICI therapy's use for treating cancers in SOTRs. However, retrospective studies have shown that ICI treatment may be associated with improved malignancy outcomes and overall survival (OS). However, the risk of allograft rejection is high (around 40%) of whom about half lose their allograft. Maintaining higher levels of immunosuppression may be associated with a lower risk of allograft rejection, but potentially worse malignancy outcomes. Summary Although ICI treatment may be associated with improved patient and malignancy outcomes, the risk of allograft rejection and loss are high. Prospective studies are needed to confirm the benefits of ICI therapy in SOTRs and to evaluate the optimal immunosuppression regimen modifications, if any, to improve patient, malignancy and allograft outcomes in transplant recipients.

Use of immune checkpoint inhibitors in solid organ transplant recipients with advanced cutaneous malignancies

“…Tailoring the immunosuppression for SOT patients receiving ICI should be carefully discussed between the oncology and transplant teams to modify risks and clinical trial participation, where able, is encouraged. In our series, patients receiving no immunosuppression had the best tumor responses whereas patients on three immunosuppressive agents were poorly responsive to ICI, consistent with other studies ( 83 , 84 ). Rates of graft failure were clearly inversely correlated with number of immunosuppressive agents, ranging from only 8.3% with 3 agents to 31.4% with one agent.…”

Metastatic Melanoma Treatment in Special Populations

“…In general, immunotherapy exposure is associated with approximately 30% to 40% allograft rejection in SOTRs who have received either monotherapy or combined therapy 7,8,10–15 . Programmed cell death 1 inhibitor monotherapy is associated with 31% to 52% allograft rejection rate, whereas CTLA-4 inhibitor monotherapy is associated with 13% to 26% allograft rejection rates 8,10–12,16,17 .…”

“…In general, immunotherapy exposure is associated with approximately 30% to 40% allograft rejection in SOTRs who have received either monotherapy or combined therapy. 7,8,[10][11][12][13][14][15] Programmed cell death 1 inhibitor monotherapy is associated with 31% to 52% allograft rejection rate, whereas CTLA-4 inhibitor monotherapy is associated with 13% to 26% allograft rejection rates. 8,[10][11][12]16,17 Data directly comparing monotherapy and combined therapy rejection rate are lacking, given small sample sizes in the few systematic reviews published, although it is widely hypothesized that combination therapy will result in a higher rejection rate.…”

“…7,8,[10][11][12][13][14][15] Programmed cell death 1 inhibitor monotherapy is associated with 31% to 52% allograft rejection rate, whereas CTLA-4 inhibitor monotherapy is associated with 13% to 26% allograft rejection rates. 8,[10][11][12]16,17 Data directly comparing monotherapy and combined therapy rejection rate are lacking, given small sample sizes in the few systematic reviews published, although it is widely hypothesized that combination therapy will result in a higher rejection rate. In one of the largest combined database and case report literature reviews on the safety and efficacy of immunotherapy in SOTRs, Cui et al 11 analyzed 168 cases from the US Food and Drug Administration Adverse Event Reporting system database in addition to 89 case reports of patients who suffered transplant rejection.…”

Urogenitale Tumoren nach Nierentransplantation – monozentrische Aufarbeitung der Inzidenzen und Überblick urologischer Vorsorgemaßnahmen

“…Aktuell stehen auch im metastasierten und lokal fortgeschrittenen Stadium gute Immuntherapeutika, auch in Kombinationen, zur NCC-Therapie zur Verfügung. Gerade für transplantierte Patienten kann hier jedoch der Benefit kaum ausgereizt werden, da bis zu 65 % einer mittels Immuntherapie behandelten Transplantationspatienten (in Studien zumeist Melanome) innerhalb von wenigen Wochen akute Transplantatrejektionen mit Transplantatverlust zeigen [ 10 , 17 , 18 ]. In derartigen Fällen muss im individuellen Gespräch mit dem Patienten ein Entscheid für oder gegen diese Möglichkeit – gerade bei funktionierendem Transplantat – getroffen werden.…”