Checkpoint Inhibitors in Kidney Transplant Recipients and the Potential Risk of Rejection

Alhamad, Tarek; Venkatachalam, Karthikeyan; Linette, Gerald P.; Brennan, Daniel C.

doi:10.1111/ajt.13711

Cited by 119 publications

(89 citation statements)

References 5 publications

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“…Although Lipson et al [51] had initially reported the successful administration of ipilimumab to 2 kidney transplantation patients with metastatic melanoma without any signs of rejection, they recently reported a case of tumor regression but allograft rejection after administration of pembrolizumab [52]. In addition, 3 cases of rejection were reported with the use of nivolumab in kidney transplant patients with melanoma [53,54,55]. Online supplementary Table 5 summarizes all 6 cases.…”

Section: Introductionmentioning

confidence: 99%

Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review

Wanchoo

Karam²,

Uppal³

et al. 2017

Am J Nephrol

11,142

256

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Background: Cancer immunotherapy, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death 1 (PD-1), has revolutionized the treatment of malignancies by engaging the patient's own immune system against the tumor rather than targeting the cancer directly. These therapies have demonstrated a significant benefit in the treatment of melanomas and other cancers. Summary: In order to provide an extensive overview of the renal toxicities induced by these agents, a Medline search was conducted of published literature related to ipilimumab-, pembrolizumab-, and nivolumab-induced kidney toxicity. In addition, primary data from the initial clinical trials of these agents and the FDA adverse reporting system database were also reviewed to determine renal adverse events. Acute interstitial nephritis (AIN), podocytopathy, and hyponatremia were toxicities caused by ipilimumab. The main adverse effect associated with both the PD-1 inhibitors was AIN. The onset of kidney injury seen with PD-1 inhibitors is usually late (3-10 months) compared to CTLA-4 antagonists related renal injury, which happens earlier (2-3 months). PD-1 as opposed to CTLA-4 inhibitors has been associated with kidney rejection in transplantation. Steroids appear to be effective in treating the immune-related adverse effects noted with these agents. Key Message: Although initially thought to be rare, the incidence rates of renal toxicities might be higher (9.9-29%) as identified by recent studies. As a result, obtaining knowledge about renal toxicities of immune checkpoint inhibitors is extremely important.

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Section: Introductionmentioning

confidence: 99%

Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review

Wanchoo

Karam²,

Uppal³

et al. 2017

Am J Nephrol

11,142

256

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“…For example, in the postrenal-transplant setting, there is an increased risk of a wide range of cancers, like Kaposi sarcoma, skin1 (non-melanoma and melanoma2 3), non-Hodgkin’s lymphoma, Hodgkin lymphoma, renal cell carcinoma, other solid tumours4 and anal cancer5 which are associated with poor prognosis. Monoclonal antibodies against CTLA-4 (Cytotoxic T-Lymphocyte Associated Protein 4) and PD-1 (Programmed cell death protein 1 ) have been used successfully to treat melanoma,2 3 non-small cell lung cancer6 and renal cell cancer 7. With the tissue agnostic indication of PD-1 inhibitors, that is, the indicated population is chosen by prior treatment history and a set of molecular markers instead of the histological tissue of origin, they can now be given to a broad range of malignancies.…”

Section: Introductionmentioning

confidence: 99%

“…In the first two reports, ipilimumab was used initially in the treatment of melanoma and the graft remained intact 7 13. As the disease progressed, the treatment was switched to pembrolizumab,7 and nivolumab13 respectively, with both undergoing graft rejection requiring haemodialysis. However, the patient on nivolumab had a good clinical response after six cycles 13.…”

Section: Introductionmentioning

confidence: 99%

“…However, the patient on nivolumab had a good clinical response after six cycles 13. Even though in case7 the rejection happened after starting pembrolizumab, there is always a possibility of rejection being actually due to the use of checkpoint inhibitors in sequence. In these cases, ciclosporin7 and tacrolimus,13 respectively, were discontinued before administering ipilimumab and were maintained on prednisone.…”

Section: Introductionmentioning

confidence: 99%

“…Even though in case7 the rejection happened after starting pembrolizumab, there is always a possibility of rejection being actually due to the use of checkpoint inhibitors in sequence. In these cases, ciclosporin7 and tacrolimus,13 respectively, were discontinued before administering ipilimumab and were maintained on prednisone. In the next two reports, patients with melanoma were treated with pembrolizumab,6 and nivolumab 14.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Immune checkpoint inhibitors in the management of malignancies in transplant recipients

Regalla

Williams

Paluri

2018

Postgraduate Medical Journal

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Cancer immunotherapy, an area of active research, has thus far yielded several exciting breakthroughs in cancer treatment strategies. So far, immune checkpoint inhibitors have been the most promising method of cancer immunotherapy. CTLA-4, PD-1 and PD-L1 are the immune checkpoint molecules against which monoclonal antibodies act against and revolutionised the treatment of several malignancies. However, it is still unclear whether using these monoclonal antibodies in patients with malignancy and a history of transplant is as beneficial as in patients without a history of transplantation. The reason being, with the therapeutic benefit, also comes the inherent disadvantage of transplant rejection because of the activation of T-cells against donor antigens. So, transplant-related complications limit the usage of the checkpoint blockade therapy to treat malignancies. Here, we review the data published in this context and suggest optimal approaches to using the currently available repertoire of immunotherapies.

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