Safety and efficacy of CAR-T cell targeting BCMA in patients with multiple myeloma coinfected with chronic hepatitis B virus

Abstract

BackgroundReactivation 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).MethodsWe administered B cell maturation antigen (BCMA) CAR-T cell by infusion to nine patients with R/R MM 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.ResultsIn one patient who was HBsAg-positive, 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).ConclusionsThese findings showed that BCMA CAR-T cell therapy could be used in patients with R/R MM with chronic or resolved HBV infection and that antiviral drugs should be administered in these patients during CAR-T cell therapy.

Hepatitis B virus and hepatitis C virus reactivation in cancer patients receiving novel anticancer therapies

“…In a study of patients with past HBV infection treated with CAR T-cell therapy [50], one of nine patients with multiple myeloma (1 chronic HBV and 8 past HBV) developed viral reactivation (HBsAg reverse seroconversion) without detection of HBV DNA or hepatic failure. This patient was not receiving antiviral prophylaxis, but entecavir was started when reactivation occurred followed by HBsAg loss after 2 months of entecavir.…”

Risk of HBV Reactivation in Patients With Resolved HBV Infection Receiving Anti-CD19 Chimeric Antigen Receptor T Cell Therapy Without Antiviral Prophylaxis

“…Strati P. reported a case of HBV reactivation after discontinuing antiviral prophylaxis in a DLBCL patient with HBsAg−/HBcAb+ at baseline receiving axicabtagene ciloleucel (17). Han et al reported a case of HBV reactivation in eight patients with multiple myeloma and resolved HBV infection receiving CAR-T cells targeting BCMA (18). In contrast, three case series reported no reactivation among HBsAg−/HBcAb+ patients treated with single CART19 cell therapy (19)(20)(21).…”

The Application of Nanobody in CAR-T Therapy

“…Two independent nanobody modules targeting BCMA have been developed and demonstrated their significant clinic effects on relapse/refractory multiple myeloma. One project has been developed by Pregene Biopharma and its CAR construct has been composed of a monovalent anti-BCMA nanobody, 4-1BB and CD3ζ (PRG1801) [ 77 ]. The other anti-BCMA CAR was constructed by Nanjing Legend Biotech, which employed two nanobodies recognizing BCMA in a bi-epitopic manner [ 75 , 76 ].…”

“…Another anti-BCMA nanobody-based CAR-T with a 2nd-generation CAR, PRG1801, has been used to treat 34 patients in a clinical study (NCT03661554). Within the median follow-up time of 12.5 months, 30 patients, representing 88.2%, had the best overall response, and 19 (55.9%) of them achieved complete remission [ 77 , 108 ].…”

“…Nanobodies have demonstrated their potential and feasibility in the discovery and development of CAR-T therapies. PRG1801 is composed of a monovalent anti-BCMA nanobody, 4-1BB, and CD3ζ [77,108], while the other anti-BCMA CAR-T developed by Nanjing Legend Biotech employed two nanobodies recognizing BCMA in a bi-epitopic manner [75,76,109,110]. Based on the published data, their clinical effects are both comparable to that of bb2121, which was developed by Bluebird with the use of an scFv targeted Besides fourth-generation CAR-T with the secretion of cytokines, many have been paid to explore the variable formats of antibody secretion with the use of NanoCAR-T therapies, as listed in Table 2.…”