PMID- 36191571 OWN - NLM STAT- MEDLINE DCOM- 20221018 LR - 20221108 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 175 DP - 2022 Nov TI - Immune checkpoint blockade for organ-transplant recipients with cancer: A review. PG - 326-335 LID - S0959-8049(22)00487-7 [pii] LID - 10.1016/j.ejca.2022.08.010 [doi] 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. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Runger, Alessandra AU - Runger A AD - Department of Dermatology and Venereology, University Hospital Hamburg-Eppendorf (UKE), Hamburg, Germany. Electronic address: a.ruenger@uke.de. FAU - Schadendorf, Dirk AU - Schadendorf D AD - Department of Dermatology, University Hospital Essen, Essen, Germany. Electronic address: Dirk.Schadendorf@uk-essen.de. FAU - Hauschild, Axel AU - Hauschild A AD - Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany. Electronic address: ahauschild@dermatology.uni-kiel.de. FAU - Gebhardt, Christoffer AU - Gebhardt C AD - Department of Dermatology and Venereology, University Hospital Hamburg-Eppendorf (UKE), Hamburg, Germany. Electronic address: ch.gebhardt@uke.de. LA - eng PT - Journal Article PT - Review DEP - 20220930 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 0 (Immune Checkpoint Inhibitors) RN - 0 (Immunosuppressive Agents) RN - 0 (MTOR Inhibitors) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Graft Rejection MH - Humans MH - Immune Checkpoint Inhibitors/therapeutic use MH - Immunosuppressive Agents/therapeutic use MH - MTOR Inhibitors MH - *Neoplasms/chemically induced/drug therapy MH - TOR Serine-Threonine Kinases MH - *Transplant Recipients OTO - NOTNLM OT - Immune checkpoint inhibitors OT - Immunosuppression OT - Transplant OT - Tumour response OT - mTOR inhibitor COIS- Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dirk Schadendorf received honoraria from Roche/Genentech, Novartis, Bristol-Myers Squibb, Merck Sharp & Dohme, Immunocore, Merck Serono, Array BioPharma, Pfizer, Pierre Fabre, Philogen, Regeneron, 4SC, Sanofi/Regeneron, Neracare, Sun Pharma, Inflarx GmbH, Ultimovacs, Sandoz, Amgen, Daiichi Sankyo Japan, LabCorp, Nektar and Replimune, reports consulting/advisory role for Roche/Genentech, Novartis, Bristol-Myers Squibb, Merck Sharp & Dohme, Merck Serono, 4SC, Pierre Fabre, Philogen, Sanofi/Regeneron, Ultimovacs and Nektar, speaker's bureau for Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi/Regeneron and Merck KGaA, received research funding from Bristol-Myers Squibb, Novartis, Roche, MSD Oncology, Array/Pfizer and Amgen, and received Travel/accommodations/expenses from Roche/Genentech, Bristol-Myers Squibb, Merck Serono, Novartis, Merck Sharp & Dohme, Pierre Fabre and Sanofi/Regeneron. Axel Hauschild reports grants and personal fees from Amgen, BMS, Eisai, Immunocore, MerckPfizer, MSD/Merck, Novartis Pharma, Philogen, Pierre Fabre, Regeneron, Replimune, Roche, Sanofi-Genzyme, and Seagen. Christoffer Gebharft is a member of the advisory board of, and has received honoraria and travel expenses by Almirall, Amgen, Beiersdorf, BioNTech, Bristol-Myers Squibb, Immunocore, Janssen, MSD Sharp & Dohme, Novartis, Pierre-Fabre, Roche, Sanofi Genzyme, SUN Pharma, Sysmex/Inostics; CG holds shares of Dermagnostix and Dermagnostix R&D. All remaining authors declare no conflicts of interest. EDAT- 2022/10/04 06:00 MHDA- 2022/10/19 06:00 CRDT- 2022/10/03 18:32 PHST- 2022/07/06 00:00 [received] PHST- 2022/08/02 00:00 [revised] PHST- 2022/08/05 00:00 [accepted] PHST- 2022/10/04 06:00 [pubmed] PHST- 2022/10/19 06:00 [medline] PHST- 2022/10/03 18:32 [entrez] AID - S0959-8049(22)00487-7 [pii] AID - 10.1016/j.ejca.2022.08.010 [doi] PST - ppublish SO - Eur J Cancer. 2022 Nov;175:326-335. doi: 10.1016/j.ejca.2022.08.010. Epub 2022 Sep 30.