Safety and Efficacy of CAR-T Cell Targeting BCMA in Patients with Multiple Myeloma Co-Infected with Chronic Hepatitis B Virus

Abstract

Background: Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication in patients with chronic or resolved HBV infection undergoing anticancer therapy. There is a risk of HBV reactivation after infusion of chimeric antigen receptor (CAR) T cells for patients with refractory/relapsed (R/R) multiple myeloma (MM). Methods: We administered B cell maturation antigen (BCMA) CAR-T cells by infusion to nine R/R MM patients with chronic or resolved HBV infection. Patient serum was analyzed to determine the expression of five components of HBV and the copy number of HBV DNA. HBV reactivation was defined if a patient re-exhibited hepatitis B surface antigen (HBsAg) or HBV DNA regrowth after CAR-T therapy. Findings: In one HBsAg-positive patient, no HBV reactivation was observed during the follow-up period of 9.8 months after administration of anti-HBV drugs before and after CAR-T therapy. Among eight patients with MM who had resolved HBV infection, two patients administered prophylactic anti-HBV drugs did not exhibit HBV reactivation. Of the six patients who did not use prophylactic antiviral drugs, five did not exhibit HBV reactivation, while one showed recurrence of HBsAg without detection of HBV DNA or damage to liver function. The best objective response rate was 100%, and the progression-free survival (PFS) at 12 months was of 88.89% (median PFS was not observed). Interpretation: These findings showed that BCMA CAR-T cell therapy could be used in R/R MM patients with chronic or resolved HBV infection and that antiviral drugs should be administered in these patients during CAR-T cell therapy. Trial Registration: This study was conducted at the Affiliated Cancer Hospital of Zhengzhou University and was registered with clinicaltrials.gov (registration number: NCT03664661). Funding Statement: This study was supported by grants from Henan Medical Science and Technique Foundation (grant number 2018020484; SBGJ2018085); Henan Provincial Scientific and technological project (grant number 162300410095); Natural Science Foundation of Henan (grant number 182300410344); Henan province industry-university-research cooperation project (grant number 182107000027). Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The study protocol was approved by the Ethics Committee of the Affiliated Cancer Hospital of Zhengzhou University. Informed consent was obtained from all patients.