Checkpoint inhibitor therapy for cancer in solid organ transplantation recipients: an institutional experience and a systematic review of the literature
Open accessAbstract
BACKGROUND: Checkpoint inhibitors (CPIs) have revolutionized the treatment of cancer, but their use remains limited by off-target inflammatory and immune-related adverse events. Solid organ transplantation (SOT) recipients have been excluded from clinical trials owing to concerns about alloimmunity, organ rejection, and immunosuppressive therapy. Thus, we conducted a retrospective study and literature review to evaluate the safety of CPIs in patients with cancer and prior SOT. METHODS: Data were collected from the medical records of patients with cancer and prior SOT who received CPIs at The University of Texas MD Anderson Cancer Center from January 1, 2004, through March 31, 2018. Additionally, we systematically reviewed five databases through April 2018 to identify studies reporting CPIs to treat cancer in SOT recipients. We evaluated the safety of CPIs in terms of alloimmunity, immune-related adverse events, and mortality. We also evaluated tumor response to CPIs. RESULTS: Thirty-nine patients with allograft transplantation were identified. The median age was 63 years (range 14-79 years), 74% were male, 62% had metastatic melanoma, 77% received anti-PD-1 agents, and 59% had prior renal transplantation, 28% hepatic transplantation, and 13% cardiac transplantation. Median time to CPI initiation after SOT was 9 years (range 0.92-32 years). Allograft rejection occurred in 41% of patients (11/23 renal, 4/11 hepatic, and 1/5 cardiac transplantations), at similar rates for anti-CTLA-4 and anti-PD-1 therapy. The median time to rejection was 21 days (95% confidence interval 19.3-22.8 days). There were no associations between time since SOT and frequency, timing, or type of rejection. Overall, 31% of patients permanently discontinued CPIs because of allograft rejection. Graft loss occurred in 81%, and death was reported in 46%. Of the 12 patients with transplantation biopsies, nine (75%) had acute rejection, and five of these rejections were T cell-mediated. In melanoma patients, 36% responded to CPIs. CONCLUSIONS: SOT recipients had a high allograft rejection rate that was observed shortly after CPI initiation, with high mortality rates. Further studies are needed to optimize the anticancer treatment approach in these patients.
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In this report, tumor response was documented in 40% of patients who experienced allograft rejection and 52% of those who did not.
“Noteworthy, in this report tumor response was documented 40% of patients who experienced allograft rejection and 52% of those who did not.155,156”
From Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy (2020) · cites this paper as [155]
A recent systematic review and institutional experience report including 39 ICI-treated transplant recipients (23 renal, 11 hepatic, 5 cardiac) reported allograft rejection in 41% of patients [11 renal (48%), 4 hepatic (36%), 1 cardiac (20%)] with very similar rates between anti-PD-1 versus anti-CTLA-4 agents (40% versus 36%).
“Interestingly, a recent systematic review and institutional experience report 155 that included 39 ICI-treated transplant recipients (23 renal, 11 hepatic, 5 cardiac) reported allograft rejection in 41% of patients [11 renal (48%), 4 hepatic (36%), 1 cardiac (20%)] with very similar rates between anti-PD-1 versus anti-CTLA-4 agents (40% versus 36%).”
From Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy (2020) · cites this paper as [155]
The median time to kidney allograft rejection was 21 days after ICI initiation (95% confidence interval, 19.3, 22.8 days).
“The median time to kidney allograft rejection was 21 days after ICI initiation (95% confidence interval, 19.3, 22.8 days).”
From Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy (2020) · cites this paper as [155]
In a recent study, 13 of 16 (81%) patients with allograft failure experienced graft loss despite aggressive treatment with high-dose corticosteroids and immunosuppression intensification with the addition of sirolimus, TMS, MMF, or IVIG.
“Furthermore, in this recent study, 13 of the 16 (81%) patients with allograft failure experienced graft loss despite aggressive treatment with high-dose CS 155 and immunosuppression intensification with the addition of sirolimus, TMS, MMF, or IVIG.155,174”
From Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy (2020) · cites this paper as [155]
Authors suggest a possible difference in immune mechanisms mediating the occurrence of immune-related adverse events and allotransplantation immunity because they observed an irAEs rate similar to the cohort exempt from rejection and to the classical rate obtained in non-SOT recipients.
“Authors also suggest a possible difference in immune mechanisms mediating the occurrence of irAEs and allotransplantation immunity because they observed an irAEs rate similar to the cohort exempt from rejection and to the classical rate obtained in non-SOT recipients.”
From Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy (2020) · cites this paper as [155]
The risk in transplant recipients may be due to alloimmunity and acute rejection of the allograft, rather than an ICI-induced immune-mediated adverse event.
“So far, they consider whether the risk in transplant recipients may be due to alloimmunity and acute rejection of the allograft, rather than an ICI-induced imAE.155”
From Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy (2020) · cites this paper as [155]
Cancer immunotherapy results in organ rejection in the majority of patients with renal transplants who are candidates for ICIs.
“Cancer immunotherapy results in organ rejection in the majority of these patients, requiring more immunosuppression to prevent allograft rejection and graft loss7–9.”
From Targeting the mTOR pathway uncouples the efficacy and toxicity of PD-1 blockade in renal transplantation (2019) · cites this paper as [8]
Key recent reviews of all transplant cases treated with ICIs highlight the vast heterogeneity of immunosuppression regimens used and the void of translational data guiding treatment decisions.
“Key recent reviews of all the transplant cases treated with ICIs highlight the vast heterogeneity of the immunosuppression regimens used in this setting the void of any translational data guiding treatment decisions7–9.”
From Targeting the mTOR pathway uncouples the efficacy and toxicity of PD-1 blockade in renal transplantation (2019) · cites this paper as [8]
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Self-citation
- Authors
- Abdel-Wahab, N., Safa, H., Abudayyeh, A., Johnson, D. H., Trinh, V. A., Zobniw, C. M., Lin, H., Wong, M. K., Abdelrahim, M., Gaber, A. O., Suarez-Almazor, M. E., & Diab, A.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Houston Methodist (US)
- Corresponding author
- Diab, Adi
- ORCID
- Venue
- Journal for ImmunoTherapy of Cancer
- Publisher
- BMJ
- Published
- 2019-04-16
- Volume
- 7
- Issue
- 1
- Pages
- 106-106
- ISSN
- 2051-1426 (ISSN-L)
- PMC
- PMC6469201
- OpenAlex
- W2938409495
- Cited by
- 294
- References
- 52
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 47 · 2023: 40 · 2022: 62 · 2021: 46 · 2020: 45 · 2019: 17 · 2017: 1
- FWCI
- 4.05
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-06-24)
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal for ImmunoTherapy of Cancer (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- University of Texas MD Anderson Cancer Center (P30-CA-016672)
- Faculty of Medicine, Assiut University
- National Cancer Institute (P30CA016672)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
- Keywords
- immune checkpoint inhibitors, solid organ transplantation, allograft rejection, immune-related adverse events, anti-PD-1 therapy, CTLA-4 blockade, metastatic melanoma, graft loss, immunosuppression, cancer immunotherapy safety, kidney transplantation, liver transplantation, heart transplantation, T cell-mediated rejection, time since transplantation
- MeSH terms
- Antineoplastic Agents, Immunological, Adolescent, Adult, Aged, Female, Follow-Up Studies, Graft Rejection, Humans, Immunosuppressive Agents, Male, Middle Aged, Neoplasms, Retrospective Studies, Transplantation, Homologous, Organ Transplantation, Treatment Outcome, Risk Assessment, Young Adult, CTLA-4 Antigen, Programmed Cell Death 1 Receptor
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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