Donor-Derived Metastatic Melanoma and Checkpoint Inhibition

Boyle, S.M.; Ali, Naveed; Olszanski, Anthony J.; Park, D.J.; Xiao, Gang; Guy, Stephen R.; Doyle, A.

doi:10.1016/j.transproceed.2017.06.007

Cited by 23 publications

(18 citation statements)

References 17 publications

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“…Out of the 44 Ktx patients, 25 (59%) patients did not have a rejection. One of the patients had a transplant nephrectomy (Boyle et al 44 ) before the use of ICI, as he had donor-derived melanoma. All patients were followed for an average of 9.6 months after receiving ICI.…”

Section: Graft Tolerance Following Icismentioning

confidence: 99%

Systematic Review of the Safety of Immune Checkpoint Inhibitors Among Kidney Transplant Patients

Manohar

Thongprayoon

Cheungpasitporn

et al. 2020

Kidney International Reports

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Introduction: Kidney transplant (Ktx) recipients are excluded from clinical trials of immune checkpoint inhibitors. The aim of this systematic review was to assess the safety of immune checkpoint inhibitors among Ktx patients. Methods: A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through April 2019. We included studies that reported outcomes of Ktx recipients who received immune checkpoint inhibitors for cancer treatment. Outcomes of interest were allograft rejection and/or allograft failure. Results: Twenty-seven articles with a total of 44 Ktx patients treated with immune checkpoint inhibitor were identified. Of 44 Ktx patients, 18 were reported to have acute rejection. Median time from immune checkpoint inhibitors to acute rejection diagnosis was 24 (interquartile range, 10-60) days. Reported types of acute allograft rejection were cellular rejection (33%), mixed cellular and antibody-mediated rejection (17%), and unspecified type (50%). Fifteen (83%) had allograft failure and 8 (44%) died. Three patients had a partial remission (17%), 1 patient achieved cancer response (6%), and 5 patients had stable disease (28%). Conclusion: The findings of our study raise awareness of the increased risk for acute allograft rejection/ failure following immune checkpoint inhibitors for cancer treatment among Ktx patients, in particular with programmed cell death 1 (PD-1) inhibitors. Future large-scale clinical studies are required to appraise the pathogenesis and plan optimal balanced therapy that helps sustain graft tolerance.

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Section: Graft Tolerance Following Icismentioning

confidence: 99%

Systematic Review of the Safety of Immune Checkpoint Inhibitors Among Kidney Transplant Patients

Manohar

Thongprayoon

Cheungpasitporn

et al. 2020

Kidney International Reports

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“…20,21 There is an increasing number of reports of favorable response to checkpoint inhibition. [21][22][23][24][25] We hypothesize that older age and delaying explant by .2 years may have impaired the ability of the left kidney recipient to respond to pembrolizumab.…”

Section: Discussionmentioning

confidence: 99%

Molecular Insights in Transmission of Cancer From an Organ Donor to Four Transplant Recipients

Atreya

Collisson

Park³

et al. 2020

Journal of the National Comprehensive Cancer Network

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Organ donors are systematically screened for infection, whereas screening for malignancy is less rigorous. The true incidence of donor-transmitted malignancies is unknown due to a lack of universal tumor testing in the posttransplant setting. Donor-transmitted malignancy may occur even when not suspected based on donor or recipient factors, including age and time to cancer diagnosis. We describe the detection of a gastrointestinal adenocarcinoma transmitted from a young donor to 4 transplant recipients. Multidimensional histopathologic and genomic profiling showed a CDH1 mutation and MET amplification, consistent with gastric origin. At the time of writing, one patient in this series remains alive and without evidence of cancer after prompt organ explant after cancer was reported in other recipients. Because identification of a donor-derived malignancy changes management, our recommendation is to routinely perform short tandem repeat testing (or a comparable assay) immediately upon diagnosis of cancer in any organ transplant recipient. Routine testing for a donor-origin cancer and centralized reporting of outcomes are necessary to establish a robust evidence base for the future development of clinical practice guidelines.

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“…We speculate the five antigen-mismatch might have favored our patient’ antitumor T-cell response. It has been earlier suggested that the success of this treatment approach depends upon the degree of antigen mismatch between a tumor and the recipient; the better results were in those with the higher degree of mismatch which may offer a more reliable and robust way to develop an effective antitumor T-cell response [3, 4]. Future studies regarding mechanistic approach and therapeutics are warranted.…”

Section: Discussionmentioning

confidence: 99%

“…Novel therapy like check-point inhibitors (for instance, Ipilimumab) is changing the landscape of treatment of metastatic melanoma in the general population. However, check-point inhibitors have been successfully utilized only twice in donor-derived melanoma [2,3]. We present here, the longest disease-free survival in a patient with donor-derived melanoma with ipilimumab.…”

Section: Introductionmentioning

confidence: 91%

Successful Treatment and Five Years of Disease-free Survival in a Donor Transmitted Metastatic Melanoma with Ipilimumab Therapy

Singh¹,

Pandey²,

Rovin³

et al. 2019

Cureus

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Approximately 7% of deceased donors have unknown cancer at the time of organ procurement. More than half of these have no apparent contraindication to organ donation. The commonest transmitted malignancy is renal cell cancer (19%), followed by melanoma (17%). Donor transmission of melanoma has been fatal in most cases as it is commonly metastatic at the time of diagnosis. Till date, there have been only a few cases with remission of melanoma following transplant nephrectomy and withdrawal of immunosuppression. To our knowledge, the evidence presented here is only the second case of donor-derived melanoma that was successfully treated with Ipilimumab. Our patient has the longest disease-free survival (five years) reported in the literature to date.

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Donor-Derived Metastatic Melanoma and Checkpoint Inhibition

Cited by 23 publications

References 17 publications

Systematic Review of the Safety of Immune Checkpoint Inhibitors Among Kidney Transplant Patients

Systematic Review of the Safety of Immune Checkpoint Inhibitors Among Kidney Transplant Patients

Molecular Insights in Transmission of Cancer From an Organ Donor to Four Transplant Recipients

Successful Treatment and Five Years of Disease-free Survival in a Donor Transmitted Metastatic Melanoma with Ipilimumab Therapy

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