Cancer immunotherapy in a neglected population: The current use and future of T-cell-mediated checkpoint inhibitors in organ transplant patients

Chae, Young Kwang; Galvez, Carlos; Anker, Jonathan F.; Iams, Wade T.; Bhave, Manali

doi:10.1016/j.ctrv.2017.12.004

Cited by 40 publications

(35 citation statements)

References 38 publications

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“…[14][15][16] Median survival after diagnosis of metastasis is 3 years. 16 17 While multiple case reports and series of single agent checkpoint blockade in SOTRs exist, 18 few cases treated with concurrent ipilimumab and anti-PD1 therapy have been reported. [19][20][21] This patient exhibited partial response; however, graft rejection developed 21 days after treatment initiation.…”

Section: Introductionmentioning

confidence: 99%

Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients

Trager

Coley

Dube

et al. 2020

J Immunother Cancer

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BackgroundImmune 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 presentationsHere 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.ConclusionsThese 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.Trial Registration numberNCT03816332.

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Section: Introductionmentioning

confidence: 99%

Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients

Trager

Coley

Dube

et al. 2020

J Immunother Cancer

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“…120 PD-1 inhibition appears to be more commonly associated with graft rejection, suggesting that this pathway may play a more critical role in allograft immune tolerance. 120,124 Other factors to consider in organ transplant recipients who may be candidates for ICI therapy may include elapsed time between transplant and initiation of immunotherapy, the strength of maintenance immunosuppressive therapy required to prevent graft rejection, and the immunogenicity of the transplanted organ. 120,121 Research is underway to explore alternative immunosuppressive regimens in an effort to reduce allograft rejection during ICI therapy.…”

Section: Organ Transplant Recipientsmentioning

confidence: 99%

“…120,121 Research is underway to explore alternative immunosuppressive regimens in an effort to reduce allograft rejection during ICI therapy. 121,124 The safety and utility of immunotherapy is also being investigated in patients with multiple myeloma who may be unable to mount an adequate immune response. In KEYNOTE 183 and KEYNOTE 185, more deaths were seen for treatment arms in which pembrolizumab was added to lenalidomide/ dexamethasone or pomalidomide/dexamethasone.…”

Section: Organ Transplant Recipientsmentioning

confidence: 99%

Management of Immunotherapy-Related Toxicities, Version 1.2019, NCCN Clinical Practice Guidelines in Oncology

Thompson

Schneider

Brahmer

et al. 2019

Journal of the National Comprehensive Cancer Network

436

332

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The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions and ASCO, consisting of medical and hematologic oncologists with expertise in a wide array of disease sites, and experts from the fields of dermatology, gastroenterology, neuro-oncology, nephrology, emergency medicine, cardiology, oncology nursing, and patient advocacy. Several panel representatives are members of the Society for Immunotherapy of Cancer (SITC). The initial version of the NCCN Guidelines was designed in general alignment with recommendations published by ASCO and SITC. The content featured in this issue is an excerpt of the recommendations for managing toxicity related to immune checkpoint blockade and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to chimeric antigen receptor T-cell therapy, visit NCCN.org.

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“…Current literature notes kidney rejection in one of three patients exposed to ipilimumab alone and eight of 14 rejection episodes with PD-1 inhibitor therapy. [72][73][74][75][76][77][78] Three PD-1 inhibitor-associated rejections were previously exposed to ipilimumab without suffering a rejection episode. Rejection also occurred in one patient with combination therapy.…”

Section: Aki and Electrolyte Disordersmentioning

confidence: 99%

“…This was seen in a case where ipilumumab was associated with a lupus-like glomerulopathy. 73 Serum testing revealed the presence of antidouble-stranded DNA and antinuclear antigen antibodies, which disappeared after stopping ipilumumab and starting glucocorticoids. Second, certain tissues may normally express checkpoint receptors that then bind to anti-CPI antibodies, triggering an Pituitary cells also showed deposition of both anti-IgG2 antibody and complement 4D.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Nephrotoxicity of Cancer Immunotherapies: Past, Present and Future

Perazella

Shirali

2018

JASN

131

108

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Nephrotoxicity from cancer therapies is common and increasingly encountered in clinical practice, such that the subfield of "onco-nephrology" has emerged. Conventional chemotherapeutic drugs and novel agents targeting specific genes/proteins are effective cancer therapies but suffer from a number of adverse kidney effects. An effective avenue of cancer treatment is immunotherapy, which uses drugs that augment immune system-mediated recognition and targeting of tumor cells. As such, leveraging the immune system to target malignant cells represents an important modality in eradicating cancer. IFN and high-dose IL-2 are older immunotherapies used in clinical practice to treat various malignancies, whereas new cancer immunotherapies have emerged over the past decade that offer even more effective treatment options. The immune checkpoint inhibitors are an exciting addition to the cancer immunotherapy armamentarium. Chimeric antigen receptor T cells are also a new immunotherapy used to treat various hematologic malignancies. However, as with the conventional and targeted cancer agents, the immunotherapies are also associated with immune-related adverse effects, which includes nephrotoxicity.

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Cancer immunotherapy in a neglected population: The current use and future of T-cell-mediated checkpoint inhibitors in organ transplant patients

Cited by 40 publications

References 38 publications

Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients

Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients

Management of Immunotherapy-Related Toxicities, Version 1.2019, NCCN Clinical Practice Guidelines in Oncology

Nephrotoxicity of Cancer Immunotherapies: Past, Present and Future

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