Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients

Background Immune checkpoint blockade has emerged as a highly effective treatment for patients with metastatic melanoma and cutaneous squamous cell carcinoma. Nivolumab blocks the interactions between programmed cell death protein 1 and programmed death ligand 1 allowing for activation of a latent i...

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Main Authors: Richard Carvajal, Yvonne Saenger, Matthew Ingham, Shaheer Khan, Diana McDonnell, Megan H Trager, Shana M Coley, Geoffrey Dube, Faramarz H Samie, Larisa J Geskin, Daniel Brouder
Format: Article
Language:English
Published: BMJ Publishing Group 2020-05-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/8/1/e000908.full
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author Richard Carvajal
Yvonne Saenger
Matthew Ingham
Shaheer Khan
Diana McDonnell
Megan H Trager
Shana M Coley
Geoffrey Dube
Faramarz H Samie
Larisa J Geskin
Daniel Brouder
author_facet Richard Carvajal
Yvonne Saenger
Matthew Ingham
Shaheer Khan
Diana McDonnell
Megan H Trager
Shana M Coley
Geoffrey Dube
Faramarz H Samie
Larisa J Geskin
Daniel Brouder
author_sort Richard Carvajal
collection DOAJ
description Background Immune checkpoint blockade has emerged as a highly effective treatment for patients with metastatic melanoma and cutaneous squamous cell carcinoma. Nivolumab blocks the interactions between programmed cell death protein 1 and programmed death ligand 1 allowing for activation of a latent immune response against the malignancy. Ipilimumab binds to and blocks cytotoxic T-lymphocyte-associated protein 4, alleviating the negative regulation of T-cell activation that is mediated by that checkpoint. Combination therapy with nivolumab and ipilimumab is associated with longer overall survival at 5 years compared with nivolumab monotherapy. Solid organ transplant recipients have a significantly higher risk of malignancies compared with the general population. There is limited data surrounding the efficacy of combination immunotherapy in solid organ transplant recipients, as these patients were excluded from seminal trials due to risk of organ rejection.Case presentations Here we present four cases of combination immunotherapy in kidney transplant recipients. Three patients had metastatic melanoma, and one patient had metastatic cutaneous squamous cell carcinoma. Two patients had radiographic responses from immunotherapy, one patient had stable disease, and one patient had disease progression. Only one patient had biopsy-proven rejection. At last follow-up, three patients had functioning grafts, though one required hemodialysis after treatment, and one patient succumbed to disease, but graft function remained intact throughout her course.Conclusions These cases describe the use of ipilimumab and nivolumab combination immunotherapy for cutaneous malignancies in kidney transplant recipients. They highlight the potential to preserve kidney graft function while effectively treating the disease.
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spelling doaj-art-74a504e619b84516918d3cb0e557cb8f2025-08-20T02:49:50ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-05-018110.1136/jitc-2020-000908Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipientsRichard Carvajal0Yvonne Saenger1Matthew Ingham2Shaheer Khan3Diana McDonnell4Megan H Trager5Shana M Coley6Geoffrey Dube7Faramarz H Samie8Larisa J Geskin9Daniel Brouder1014 Herbert Irving Comprehensive Cancer Center, New York, New York, USA4Albert Einstein Cancer Center, Bronx, NY, USA6Columbia University, New York, NY, USA2 Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, New York, USA4 Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, New York, USAColumbia University Irving Medical Center, New York City, New York, USA2 Department of Pathology and Cell Biology, Division of Renal Pathology, Columbia University Irving Medical Center, New York, New York, USA3 Department of Medicine, Division of Nephrology, Columbia University Irving Medical Center, New York, New York, USA1 Department of Dermatology, Columbia University Irving Medical Center, New York, New York, USA1 Department of Dermatology, Columbia University Irving Medical Center, New York, New York, USA5 Ocean Renal Associates, Brick, New Jersey, USABackground Immune checkpoint blockade has emerged as a highly effective treatment for patients with metastatic melanoma and cutaneous squamous cell carcinoma. Nivolumab blocks the interactions between programmed cell death protein 1 and programmed death ligand 1 allowing for activation of a latent immune response against the malignancy. Ipilimumab binds to and blocks cytotoxic T-lymphocyte-associated protein 4, alleviating the negative regulation of T-cell activation that is mediated by that checkpoint. Combination therapy with nivolumab and ipilimumab is associated with longer overall survival at 5 years compared with nivolumab monotherapy. Solid organ transplant recipients have a significantly higher risk of malignancies compared with the general population. There is limited data surrounding the efficacy of combination immunotherapy in solid organ transplant recipients, as these patients were excluded from seminal trials due to risk of organ rejection.Case presentations Here we present four cases of combination immunotherapy in kidney transplant recipients. Three patients had metastatic melanoma, and one patient had metastatic cutaneous squamous cell carcinoma. Two patients had radiographic responses from immunotherapy, one patient had stable disease, and one patient had disease progression. Only one patient had biopsy-proven rejection. At last follow-up, three patients had functioning grafts, though one required hemodialysis after treatment, and one patient succumbed to disease, but graft function remained intact throughout her course.Conclusions These cases describe the use of ipilimumab and nivolumab combination immunotherapy for cutaneous malignancies in kidney transplant recipients. They highlight the potential to preserve kidney graft function while effectively treating the disease.https://jitc.bmj.com/content/8/1/e000908.full
spellingShingle Richard Carvajal
Yvonne Saenger
Matthew Ingham
Shaheer Khan
Diana McDonnell
Megan H Trager
Shana M Coley
Geoffrey Dube
Faramarz H Samie
Larisa J Geskin
Daniel Brouder
Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients
Journal for ImmunoTherapy of Cancer
title Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients
title_full Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients
title_fullStr Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients
title_full_unstemmed Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients
title_short Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients
title_sort combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients
url https://jitc.bmj.com/content/8/1/e000908.full
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