Pembrolizumab for metastatic melanoma in a renal allograft recipient with subsequent graft rejection and treatment response failure: a case report

Abstract

BackgroundTransplant patients were excluded from the pivotal phase III trials of checkpoint inhibitors in metastatic melanoma. The efficacy and toxicity profiles of checkpoint inhibitors in this cohort of patients are not well described. To the best of our knowledge, this is the first case report of a renal transplant patient with stage IV melanoma treated with a programmed cell death protein 1 checkpoint inhibitor that led to both treatment failure and renal graft rejection.Case presentationWe present a case of a 58-year-old white man with a long-standing cadaveric renal transplant who was diagnosed with a B-Raf Proto-Oncogene, Serine/Threonine Kinase wild-type metastatic melanoma. He was treated with first-line pembrolizumab but experienced subsequent graft failure and rapid disease progression.ConclusionsThis case highlights the risks associated with the administration of checkpoint inhibitors in patients with a renal transplant and on immunosuppressive therapy. More specifically, it adds to the literature indicating that, compared with the cytotoxic T-lymphocyte-associated protein 4 inhibitor ipilimumab, anti-programmed cell death protein 1 agents are more likely to lead to renal graft failure. Additionally, these novel immunotherapeutics may be ineffective in transplant patients; therefore, clinicians should be very aware of those risks and carefully consider selection of agents and full disclosure of the risks to their patients.

Ipilimumab for the treatment of advanced melanoma in six kidney transplant patients

“…After a median follow-up of 4.5 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) months, one patient achieved partial response, one had stable disease, and four had disease progression. Six French patients, three men and three women, mean age 66 years (range 44-74), all kidney transplant recipients, received ipilimumab (CTLA-4 inhibitor) for metastatic melanoma.…”

Immune checkpoint inhibitors in the management of malignancies in transplant recipients

“…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.…”

“…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. In the first case,6 the patient was on the immunosuppressive regimen (mycophenolate, tacrolimus) which was discontinued and started on a regimen of (everolimus, azathioprine) before initiating pembrolizumab and subsequently underwent graft rejection with the progression of melanoma.…”

“…In the next two reports, patients with melanoma were treated with pembrolizumab,6 and nivolumab 14. In the first case,6 the patient was on the immunosuppressive regimen (mycophenolate, tacrolimus) which was discontinued and started on a regimen of (everolimus, azathioprine) before initiating pembrolizumab and subsequently underwent graft rejection with the progression of melanoma. In the second case,14 tacrolimus and MMF (mycophenolate mofetil ) were discontinued and started on prednisone before initiating nivolumab with the patient having a graft rejection, but with partial tumour response.…”

“…In the last two cases,16 with intact graft, tacrolimus was stopped and maintenance prednisone was started many weeks before beginning ipilimumab, whereas in the patient with graft rejection, prednisone was started simultaneously with ipilimumab, therefore discontinuing immunosuppression might have contributed to graft rejection. Based on the above case reports, pembrolizumab/nivolumab usage is associated with a higher risk of renal graft complications so that ipilimumab may be a better option as the initial therapy in these patients for melanoma 6. There is a report in which a patient was on tacrolimus and prednisone immunosuppression postrenal transplant and he was given ipilimumab followed by nivolumab with good tolerance and no graft rejection, but the clinical response to melanoma is modest 17.…”