The outcome of checkpoint inhibitor therapy in patients with cancer and solid organ transplant: A systematic review of the literature.

Abstract

41 Background: Solid organ transplant recipients have been excluded from Checkpoint inhibitors (CPI) clinical trials because of the concern of allo-immunity and possible organ rejection. Methods: We searched 5 databases through September 2017. Studies describing the use of CPI to treat cancer in solid organ transplant Patients (pts), and provided detailed description of each case were included. Results: Sixteen publications met inclusion criteria, reporting on 19 cases. Median age of pts was 59 (14-77) yrs and 74% were male. Cancer types included melanoma (n=11), cutaneous squamous cell carcinoma (ca) (n=3), non-small cell lung ca and hepatocellular ca (n=2 each), and duodenal ca (n=1). Median time to start CPI after organ transplant was 11 (1-25) yrs. Nivolumab (nivo) was used in 53%, ipilimumab (ipi) in 26%, and pembrolizumab (pem) in 21%. Most pts were maintained on low dose prednisone (≤ 10 mg), mTOR inhibitors, and other immunosuppressives prior to initiating CPI. Graft rejection occurred in 10 of 19 pts (7/12 kidney, 2/5 liver, and 1/2 heart transplants), 90% after receiving anti PD-1, and CPI was discontinued. Median time to rejection was 21 (5-60) days, and obtained biopsies were suggestive of a T-cell mediated rejection process. Only a cardiac transplant recipient with a bioposy proven cellular rejection after nivo, had improved ejection fraction after pulse steroids. Aside from rejection no other immune related adverse events (irAEs) reported. Nivo re-challenge was recommended for a kidney recipient 12 weeks after the rejection process, and the pt had partial tumor response but remained on hemodialysis. Of the 9 pts who had no rejection, 4 had irAEs (hepatitis, colitis, pneumonitis, and dermatitis), including 3 who required high-dose steroids with subsequent improvement, and the remaining 5 pts did not experience any irAEs. Clinical benefit rate was 57% of all pts. Two pts with liver transplants died within 1 month of nivo treatment secondary to acute liver rejection, and 2 others died because of progressive cancer. Conclusions: CPI seem to be associated with high rate of rejection. Multi-institutional collaborative studies are warranted to enhance our understanding of the pathogenesis and plan optiomal therapy that maintain graft tolerance without dampening antitumor clinical benefits.