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Preserved Renal Allograft Function and Successful Treatment of Metastatic Merkel Cell Cancer Post Nivolumab Therapy

Singh, Priyamvada, MD1; Visger Von, Jon, MD1; Prosek, Jason, MD1; Rovin, Brad, MD1; Pesavento, Todd E., MD1; Olencki, Thomas, MD2; Pandey, Deepali, MD3

doi: 10.1097/TP.0000000000002502
Letters

1 Division of Nephrology and Comprehensive Transplant Center, Ohio State University, Columbus, OH.

2 Division of Hematology and Oncology, Ohio State University, Columbus, OH.

3 Department of Internal Medicine, Saint Vincent Hospital, Worcester, MA.

Received 23 July 2018. Revision received 9 October 2018.

Accepted 10 October 2018.

P.S., J.V.V., J.P., D.P., B.R., and T.E.P. declare no conflicts of interest. T.O. declares conflicts of interest with Pfizer, Bristol-Myers Squibb, and Regeneron.

P.S., J.V.V., J.P., T.O., D.P., B.R., and T.P. contributed to the design, analysis, and interpretation of data. P.S., J.V.V., J.P., T.O., D.P., B.R., and T.P. wrote, reviewed, and approved the article.

The case study is exempt from IRB approval.

Checkpoint inhibitors like programmed cell death-1 (PD1) are changing the way we envisage the prognostication of metastatic carcinomas. Binding of PD1 to PD1-ligand unleashes the power of naturally occurring antitumor T cells by suppressing T-cell migration, proliferation, and cytotoxic activities.1 The flipside of the interruption of the PD1-PDL1 interaction in the kidney transplant is the potential impairment of Forkhead box P3+ regulatory T cell–mediated graft tolerance leading to rejection and making these agents somewhat taboo in this population.1 We report a case of successful treatment of metastatic carcinoma with nivolumab (PD1 inhibitor) and preserved kidney function.

A 71-year-old female, status post deceased donor kidney transplant (5 of 6 HLA mismatch, 2A, 2B, and 1DR) in 2004 for autosomal dominant polycystic kidney disease and coincident native nephrectomy underwent induction with antithymoglobulin, glucocorticoid, and maintenance with tacrolimus and mycophenolate. She was diagnosed with Merkel cell cancer (January 2016) and underwent left lateral neck dissection and radiation therapy (May 2016). We discontinued tacrolimus, reduced mycophenolate to half, and initiated prednisone 5 mg/d. In December 2016, she had metastasis to liver and spine. After a lengthy discussion, we commenced nivolumab and prednisone (10 mg), and discontinued mycophenolate. Prior mammalian target of rapamycin inhibitors intolerance precluded their use. Given the literature experience of immediate rejection post-PD1 therapy, we simultaneously prepared her for peritoneal dialysis.2-5 She completed 13 cycles of nivolumab (240 mg, 3 mg/kg per month) without any significant side effects. She had a significant improvement in the quality of life with complete resolution of cancer-related pain and went from a house-confining weakness to driving and shopping on her own. At 1 year of follow-up, renal function remained stable, with negative donor-specific antibodies, a weight gain of 4 kg (52 from 48 kg), serum albumin of 4.3 g/dL, and no further progression of cancer on serial imaging. The 1-year trends of creatinine, eGFR, and urine protein/creatinine is illustrated in Figure 1.

FIGURE 1

FIGURE 1

To date, of the 5 kidney transplant recipients treated with PD1 inhibitors, 4 developed immediate acute rejection and graft loss.2-5 To our knowledge, our case is the second only in the literature of successful treatment without evidence of rejection.5 Given the history of metastatic cancer and no compelling clinical indications, we did not perform a renal biopsy. Though renal function remained stable, in the absence of a biopsy, a potential subacute rejection could not be ruled out. Both our case, and the previous successful case, underwent native nephrectomy.5 It might be mere coincidence or could be a signal to some tolerance pathways triggered by native nephrectomy.

To avoid immune-mediated side effects, we used a reduced frequency of nivolumab than general practice (monthly rather than twice monthly). This might be the possible mechanism which helped our patient in maintaining the tolerance to the transplanted kidney and avoiding rejection. The ideal dose and frequency to treat malignancy while avoiding rejection is an area of future research. The skepticism around PD1 inhibitors in renal transplant will continue given lack of supporting case reports. Based on our experience, PD1 inhibitors that are considered contraindication in renal transplantation could still be an option for a selected group of patients.

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REFERENCES

1. Maggiore U, Pascual J. The bad and the good news on cancer immunotherapy: implications for organ transplant recipients. Adv Chronic Kidney Dis. 2016;23:312–316.
2. Alhamad T, Venkatachalam K, Linette GP, et al. Checkpoint inhibitors in kidney transplant recipients and the potential risk of rejection. Am J Transplant. 2016;16:1332–1333.
3. Lipson EJ, Bagnasco SM, Moore J Jr, et al. Tumor regression and allograft rejection after administration of anti-PD-1. N Engl J Med. 2016;374:896–898.
4. Spain L, Higgins R, Gopalakrishnan K, et al. Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma. Ann Oncol. 2016;27:1135–1137.
5. Barnett R, Barta VS, Jhaveri KD, et al. Preserved renal-allograft function and the PD-1 pathway inhibitor nivolumab. N Engl J Med. 2017;376:191–192.
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