Nivolumab/Bevacizumab Combo Is Safe Following Liver Transplant in HCC

The combination of nivolumab (Opdivo) and bevacizumab (Avastin) is well tolerated with few adverse events and can be used in patients with hepatocellular carcinoma (HCC) after undergoing liver transplant. Lorenza Di Marco, PhD (candidate), of the Clinical and Experimental Medicine Program at the University of Modena and Reggio Emilia in Modena, Italy, presented these data at the American Association for Cancer Research Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer in Boston, Massachusetts.¹

Recurrence of HCC after liver transplant is difficult to manage, and tyrosine kinase inhibitors (TKIs) have some impact but survival is still poor. On the other hand, immune checkpoint inhibitors in combination with humanized monoclonal antibodies have recently been effective in tumor stabilization and survival in patients with HCC without liver transplants. Di Marco noted that immunotherapy treatment can increase the risk of liver rejection in patients with recurrent HCC who have undergone a liver transplant.²

Four of the 5 patients in the study remain on nivolumab plus bevacizumab treatment after a mean period of 36 weeks (range, 25-47). The only patient no longer on treatment died within 1 week after 1 dose of nivolumab because of rapid tumor progression.

Of the remaining 4 patients, 1 experienced moderate to severe rejection, which was resolved with 1 g of methylprednisolone per day for 3 days and then 50 mg of prednisone per day for 1 week. Investigators tapered and then stopped this additional regimen, and the patient was maintained on the combination therapy without any residual problems.

All remaining patients achieved disease stability with the nivolumab and bevacizumab combination at both hepatic and extrahepatic levels.

However, 2 patients with recurrent HCC bone localization experienced progression. Di Marco noted that this progression was very slow and both of these patients had a mean survival of 54 weeks (range, 52-56) with nivolumab plus bevacizumab therapy.

This proof-to-concept study evaluated 5 patients with recurrent HCC 2 to 8 years after liver transplant. All patients were intolerant or were with progression to TKIs. These patients received 240 mg of nivolumab every 14 days, total CT body scans every 8 weeks, and 5 mg/kg of bevacizumab every 14 days when disease progression was detected. All patients underwent blood tests for hepatic and renal function, echocardiogram tests, and a total CT body scan at baseline assessment. Patients were excluded if their blood tests revealed greater than 1.5 upper limit of normal creatinine or if their ejection fraction was less than 45%. HCC recurrence was most frequent in the bones (TABLE).

The combination displayed a tolerable safety profile. Acute allograft rejection risk was minimal and manageable. The nivolumab plus bevacizumab combination obtained a relevant and protracted stabilization in patients with hepatic or other extrahepatic localization.

_REFERENCES:

_{1. Di Marco L, Pivetti A, De Maria N, et al. PO003 combination therapy with nivolumab/bevacizumab is safe and effective in patients with recurrent hepatocellular carcinoma after liver transplant. Present at: American Association for Cancer Research Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; May 5-8, 2022; Boston, MA.}

_{2. Au KP, Chok KSH. Immunotherapy after liver transplantation: Where are we now?. World J Gastrointest Surg. 2021;13(10):1267-1278. doi:10.4240/wjgs.v13.i10.1267}