Immune Checkpoint Inhibitor Use in Solid Organ Transplant Recipients: A Systematic Review

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Andrew J. Portuguese University of Washington,
Fred Hutchinson Cancer Research Center, and

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Scott S. Tykodi University of Washington,
Fred Hutchinson Cancer Research Center, and

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 MD, PhD
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Christopher D. Blosser University of Washington,
Seattle Children’s Hospital, Seattle, Washington.

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Ted A. Gooley Fred Hutchinson Cancer Research Center, and

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John A. Thompson University of Washington,
Fred Hutchinson Cancer Research Center, and

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Evan T. Hall University of Washington,
Fred Hutchinson Cancer Research Center, and

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Chronic immunosuppression in solid organ transplant recipients (SOTRs) leads to an increased risk of a wide variety of cancers. Immune checkpoint inhibitor (ICI) therapy is indicated for many of these; however, the risks and benefits of ICI use in the SOTR population have not been well characterized. We performed a systematic literature review identifying 119 reported cases of ICI use among SOTRs. Treatments used included PD-1 inhibition (75.6%), CTLA-4 inhibition (12.6%), PD-L1 inhibition (1.7%), and combination and/or sequential ICI therapy (10.1%). The most common cancers included cutaneous melanoma (35.3%), hepatocellular carcinoma (22.7%), and cutaneous squamous cell carcinoma (18.5%). The overall objective response rate (ORR) was 34.5%, with a median duration of response of 8.0 months. Ongoing response was seen in 21.0%. Cutaneous squamous cell carcinoma had significantly better ORR compared with other cancer types (68.2% vs 26.8%; odds ratio [OR], 5.85; P =.0006). Factors associated with improved ORR included increasing time from transplant to ICI (OR, 1.09; P =.008) and preemptive reduction in intensity of the graft maintenance immunosuppressive regimen (50.0% vs 18.5%; OR, 4.40; P =.0088). Rejection occurred in 41.2%, graft failure in 23.5%, and immune-related adverse events in 18.5%. Factors significantly associated with allograft rejection included allograft PD-L1 positivity (100% vs 0%; P<.0001) and absence of tacrolimus in the immunosuppressive regimen (48.7% vs 25.6%; OR, 0.36; P =.019). The most common cause of death was progressive malignancy (64.0%), followed by graft failure (24.0%). Our analysis provides current benchmark data to help inform management of SOTRs with advanced cancers that are reflected by our patient cohort. Biomarker development, more robust datasets, and prospective study of concomitant immunosuppression management may help refine decision-making in this complex scenario in the future. Close coordination of care between the medical oncologist and transplant specialist is encouraged to help optimize treatment outcomes.

Submitted December 17, 2021; accepted for publication February 10, 2022.

Disclosures: Dr. Portuguese has disclosed receiving support from an institutional training grant from the National Heart, Lung, and Blood Institute (T32 HL007093). Dr. Tykodi has disclosed receiving grant/research support from AVEO Oncology, Bristol-Myers Squibb, Merck & Co., Genentech, Pfizer, Njtar Therapeutics, Exelixis, and Jounce Therapeutics; receiving consulting fees from PLS Group Services, Exelixis, Merck & Co., Bristol-Myers Squibb, and Intellisphere LLC; serving on an advisory board for Merck & Co., Exelixis, and Bristol-Myers Squibb; receiving honoraria from Natera and General Dynamics Information Technology; and serving as a consultant for Targeted Oncology. Dr. Blosser has disclosed serving as a consultant for Natera LLA, and participating in research for Natera, LLC, and CareDx Inc. Dr. Hall has disclosed serving as a principal investigator for Neoleukin Therapeutics, ImCheck Therapeutics, Checkpoint Pharmaceuticals, and Nektar. The remaining authors have disclosed no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.

Correspondence: Andrew J. Portuguese, MD, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Mail Stop D5-126, Seattle, WA 98109. Email: aportugu@uw.edu

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