Immune checkpoint blockade for organ-transplant recipients with cancer: A review

TY - JOUR

T1 - Immune checkpoint blockade for organ-transplant recipients with cancer: A review

AU - Rünger, Alessandra

AU - Schadendorf, Dirk

AU - Hauschild, Axel

AU - Gebhardt, Christoffer

N1 - Copyright © 2022 Elsevier Ltd. All rights reserved.

PY - 2022/11

Y1 - 2022/11

N2 - Clinical trials studying immune checkpoint inhibitors (ICIs) have excluded immunocompromised patients, and little is known about the safety and efficacy of immunotherapy for malignancies in this subset of patients. Transplant organ recipients receiving ICIs face two distinct challenges: First, immunotherapy may counteract immunosuppression and with that result in transplant rejection. Second, immunosuppression may make immunotherapy less effective. It remains unclear as to how commonly these seemingly opposing treatment goals, immunosuppression for organ retention and immune stimulation for effective immunotherapy, can be balanced to achieve favourable outcomes. Given a lack of prospective clinical trials, we reviewed the existing literature on this subject (case reports, case series and previous reviews) and present here an updated analysis of treatment outcomes from a total of 144 patients. This is, to our knowledge, the most extensive review on this topic available today. We found that an ideal outcome, meaning effective immunotherapy with retained transplant was achieved in 30.8% of patients. The overall response rates of immunotherapy were similar to non-immunocompromised cancer patients in the reported cases, but publication bias may overestimate positive outcomes. Contrary to expectation, tumour response rates were higher, albeit not significantly, in patients who were able to retain their transplanted organ, suggesting that it is possible to uncouple immunosuppression and immune stimulation in these patients. One possible strategy towards this goal may be to use mammalian target of rapamycin (mTOR) inhibitors for immunosuppression, as patients whose immunosuppressive regimen included an mTOR inhibitor had a 1.4-fold higher rate of ideal outcomes (n.s.). Our data support a first line treatment approach that aims for maintaining transplanted organs during ICI treatment.

AB - Clinical trials studying immune checkpoint inhibitors (ICIs) have excluded immunocompromised patients, and little is known about the safety and efficacy of immunotherapy for malignancies in this subset of patients. Transplant organ recipients receiving ICIs face two distinct challenges: First, immunotherapy may counteract immunosuppression and with that result in transplant rejection. Second, immunosuppression may make immunotherapy less effective. It remains unclear as to how commonly these seemingly opposing treatment goals, immunosuppression for organ retention and immune stimulation for effective immunotherapy, can be balanced to achieve favourable outcomes. Given a lack of prospective clinical trials, we reviewed the existing literature on this subject (case reports, case series and previous reviews) and present here an updated analysis of treatment outcomes from a total of 144 patients. This is, to our knowledge, the most extensive review on this topic available today. We found that an ideal outcome, meaning effective immunotherapy with retained transplant was achieved in 30.8% of patients. The overall response rates of immunotherapy were similar to non-immunocompromised cancer patients in the reported cases, but publication bias may overestimate positive outcomes. Contrary to expectation, tumour response rates were higher, albeit not significantly, in patients who were able to retain their transplanted organ, suggesting that it is possible to uncouple immunosuppression and immune stimulation in these patients. One possible strategy towards this goal may be to use mammalian target of rapamycin (mTOR) inhibitors for immunosuppression, as patients whose immunosuppressive regimen included an mTOR inhibitor had a 1.4-fold higher rate of ideal outcomes (n.s.). Our data support a first line treatment approach that aims for maintaining transplanted organs during ICI treatment.

KW - Graft Rejection

KW - Humans

KW - Immune Checkpoint Inhibitors/therapeutic use

KW - Immunosuppressive Agents/therapeutic use

KW - MTOR Inhibitors

KW - Neoplasms/chemically induced

KW - TOR Serine-Threonine Kinases

KW - Transplant Recipients

U2 - 10.1016/j.ejca.2022.08.010

DO - 10.1016/j.ejca.2022.08.010

M3 - SCORING: Review article

C2 - 36191571

VL - 175

SP - 326

EP - 335

JO - EUR J CANCER

JF - EUR J CANCER

SN - 0959-8049

ER -