Extending the Use of Atezolizumab and Bevacizumab to a Liver Transplant Recipient: Need for a Posttransplant Registry

Max Seidensticker consults, advises, and has received grants from Bayer, Cook, and Sirtex. Daniel Roessler advises for Bayer and advises and has received grants from Ipsen. Najib Ben Khaled has received a travel grant from Eisai and lecture honoraria from Falk. Prof. De Toni has served as a paid consultant for AstraZeneca, Bayer, BMS, Eisai, Eli Lilly, Pfizer, Ipsen and Roche. He has received reimbursement of meeting attendance fees and travel expenses from Arqule, BMS, Bayer, Celsion and Roche, and lecture honoraria from BMS, Falk and Roche. He has received third‐party funding for scientific research from Arqule, AstraZeneca, BMS, Bayer, Eli Lilly and Roche. TO THE EDITOR: We read with interest the article by Bhangui et al. who provide a model of prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) from a living donor.(1) The still frequent post‐LT recurrence of HCC raises the controversial issue of the use of immunotherapy in LT recipients, a topic that has gained exceptional relevance after the combination of atezolizumab/bevacizumab has been approved for the treatment of HCC. Checkpoint‐inhibitor based combination regimens have been shown high efficacy in advanced HCC,(2) but little is known about the activity and safety of immunotherapy after LT. The availability of these immunotherapeutic agents for treatment of HCC will cause clinicians to be increasingly called to weigh the potential oncological benefits of immunotherapy in transplant recipients against the odds of a fatal treatment outcome owing to the potential occurrence of organ rejection. We recently used atezolizumab/bevacizumab in analogy to the Imbrave150 study as a salvage treatment for a 35‐year‐old male patient with a recurrence of fibrolamellar HCC 4 years after LT.(2) Treatment was initiated after multiple surgical and local interventions and after the failure of 2 regimens of systemic therapy (gemcitabine/oxaliplatin and fluorouracil/interferon alfa‐2b). A positron emission tomography–computed tomography scan conducted after 3 months of treatment showed a marked decrease of [18F]fludeoxyglucose uptake as a possible sign of response (Fig. 1). Because therapy was well tolerated, and, notably, no signs of organ rejection were evident, atezolizumab/bevacizumab was continued for an additional 6 months until diffuse disease progression and clinical deterioration became evident. The patient died 10 months after treatment initiation as a result of tumor progression without signs of immune‐mediated liver toxicity (Supporting Fig. 1 and Table 1).FIG. 1: [18F]fludeoxyglucose positron emission tomography/computed tomography scans (A,C) before and (B,D) 3 months after initiation of atezolizumab/bevacizumab. Arrows indicate representative lesions with decreasing metabolic activity.The approval of atezolizumab/bevacizumab marked a breakthrough in the therapy of HCC. However, the experience on the use of these agents in the post‐LT setting is limited to case series.(3) This is the first report on the use of combined atezolizumab/bevacizumab, the now standard first‐line treatment of advanced HCC, in a LT recipient. This case shows that organ rejection does not invariably occur in LT recipients receiving immunotherapy even when used in combinations intended to enhance immune response. Immunotherapy cannot be recommended in LT recipients. Nevertheless, after the approval of atezolizumab/bevacizumab, an increasingly frequent use of these agents as a salvage treatment of post‐LT HCC recurrence is to be expected. Until biomarkers capable of predicting response or liver toxicity will become available, we propose that an international registry is established to collect evidence from single‐case experiences on the effects of immunotherapy in the posttransplant setting to guide future clinical studies.