Abstract 1985: Ipilimumab and nivolumab induced reactivation of hepatitis B (HBVr) in patient with metastatic squamous cell lung cancer
Authors: Kim Leeseul , Choi Horyun , Lee Yeun Ho , Kim Jinah , Chae Young Kwang 
Published: June 2022

Background: Unique adverse events caused by immunological perturbation of immune checkpoint inhibitor (ICI) treatment were reported. Recently, it came into light that ICI can increase the risk of HBVr. Immune-mediated adverse events including immune-mediated hepatitis have been widely reported. However, HBVr is an extremely rare adverse event that has been seldom reported. Herein, we report the first case of ipilimumab/nivolumab induced HBVr in metastatic squamous cell lung cancer patient.

Case Presentation: 71-year-old Asian gentlemen with stage IIIB poorly differentiated squamous cell carcinoma of the lung (PD-L1 immunohistochemistry 5-10%) was initially treated with 4 cycles of carboplatin/paclitaxel/pembrolizumab and one dose of maintenance pembrolizumab. The treatment was complicated by immune-related adverse events of thyroiditis and adrenal insufficiency and followed by surgical resection of the tumor. Unfortunately, he developed recurrent metastatic disease of the brain which provoked craniotomy and resection followed by multiple courses of radiation therapy. The patient was then started on treatment with ipilimumab/nivolumab maintenance therapy following 2 cycles of carboplatin/paclitaxel/nivolumab/ipilimumab combined therapy (every 3 weeks). Bevacizumab was added for cerebral edema associated with brain metastasis. The patient was initially noted to be positive for hepatitis B Antigen. However, he was asymptomatic and liver function test (LFT) and liver ultrasound were unremarkable. He had been monitored for LFT at every visit. After 5.5 months from starting the treatment (after seven cycles of ipilimumab/nivolumab and six cycles of bevacizumab), transaminitis was noted and treatment was held. He was admitted for abdominal pain with labs demonstrating hepatocellular injury with ALT 1761 units/L, AST 607 units/L, and total bilirubin 3.3 mg/dL. Hepatitis work-up revealed HBVr (positive for HBs Ag, hepatitis B viral load 11,745). Patient was started on tenofovir daily and LFT was normalized after three weeks without synthetic dysfunction or metabolic encephalopathy. Ipilimumab/nivolumab treatment was held for six weeks and reintroduced without any further significant events.

Conclusion: It has recently been reported that pembrolizumab had a strong signal associated with HBVr. However, to our knowledge, this is the first case report for HBVr in squamous cell carcinoma of lung patient treated with ipilimumab/nivolumab. ASCO recommends universal screening for hepatitis B for patients anticipating systemic anticancer therapy. As illustrated by our case, it is important to have hepatitis B screening before starting systemic therapy including immunotherapy. Additional larger studies are warranted to validate the role of each type of ICI in HBVr.

Citation Format: Leeseul Kim, Horyun Choi, Yeun Ho Lee, Jinah Kim, Young Kwang Chae. Ipilimumab and nivolumab induced reactivation of hepatitis B (HBVr) in patient with metastatic squamous cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1985.