The Risk of Hepatitis B Reactivation Is Controllable in Patients with Concomitant Hepatitis B Virus Infection during Chimeric Antigen Receptor T-Cell Therapy
Authors: Liu Wei , Lv Rui , Huang Wenyang , Liu Hong , Deng Shuhui , Yi Shuhua , Lv Lulu , Wang Jianxiang , Qiu Lugui , Zou Dehui 
Published: November 2019

Background: Among patients with non-Hodgkin lymphoma (NHL) and concomitant chronic or resolved hepatitis B virus (HBV) infection, HBV reactivation is an identified risk associated with chemotherapy, especially after rituximab-based immunochemotherapy. Chimeric antigen receptor (CAR) T-cell targeting CD19 can also cause B-cell aplasia as seen in patients receiving rituximab, and the risk of HBV reactivation during CAR T-cell therapy is still unknown. We performed a retrospective study to explore the risk of HBV reactivation in patients with concomitant HBV infection who had received anti-CD19 CAR T therapy at our hospital.
Methods: Patients with relapse or refractory B-cell lymphoma who were treated with CNCT19 (second-generation anti-CD19 CAR T-cell provided by Juventas) at Blood Disease Hospital were retrospectively analyzed. All patients were screened for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb) at the time of evaluation for CNCT19 therapy, and those with positive HBsAg or positive HBcAb were eligible for this retrospective study. This study was approved by Blood Diseases Hospital Internal Review Board.
Results: Between June 2017 and May 2019, 17 patients with relapsed or refractory B-cell lymphoma and concomitant HBV infection who were treated with CNCT19 therapy alone (n=14) or CNCT19 therapy following high-dose chemotherapy and autologous stem cell transplantation (HDT/ASCT, n=3) were included in this study. The median age was 53 years (range: 31-71years), with 53% were male. 6 patients (35%) had chronic HBV infection, defined as positive HBsAg, 11 patients (65%) had resolved HBV infection, defined as negative HBsAg and positive HBcAb. At the time of CNCT19 infusion, HBV DNA levels of all patients were lower than the normal limit (<1000IU/ml). All 6 patients with chronic HBV infection received prophylactic anti-HBV nucleos(t)ide therapy (NAT) of entecavir, 5/11(45%) patients with resolved HBV infection received prophylactic NAT of entecavir or lamivudine, and the other 6/11(55%) patients with resolved HBV infection did not receive any prophylactic anti-HBV therapy. With median follow-up of 8 months (range: 1-24 months) from CNCT19 infusion, including 9 patients who had been followed up for more than 6 months, no HBV reactivation occurred (defined as HBV-DNA level exceeding 1000IU/ml). 6 patients with chronic HBV infection remained on NAT at the time of last follow-up, and among the 5 patients with resolved HBV infection who had received prophylactic NAT during CNCT19 therapy, 1 patient was still on NAT at 3 months after CNCT19 infusion following HDT/ASCT, 4 patients stopped NAT at 1, 2, 6, 6months after CNCT19 infusion, respectively. Cytokine release syndrome (CRS) occurred in 59% of patients and CAR-T-cell-related encephalopathy syndrome (CRES) occurred in 12% of patients, with 2 patients received short term of corticosteroids for grade 4 CRES.
Conclusions: Our results showed that CAR T therapy could be safely administered in patients with chronic or resolved HBV infection. Considering the small sample size and the retrospectively analysis, the risk of HBV reactivation and the recommendation for prophylactic anti-HBV NAT during CAR T therapy should be further evaluated in large and prospective studies.

Disclosures
Lv: Juventas Cell Therapy Ltd.: Employment.