Severe early hepatitis B reactivation in a patient receiving anti-CD19 and anti-CD22 CAR T cells for the treatment of diffuse large B-cell lymphoma

Abstract

Background: Hepatitis B virus (HBV) reactivation is commonly seen in HBsAg-positive hematologic patients undergoing immunosuppressive chemotherapy. Little is known about the risk of HBV reactivation after chimeric antigen receptor T-cell (CAR T) immunotherapy for the treatment of refractory/relapsed malignant B-cell lymphoma.

Case presentation: We report a patient who underwent antiviral prophylaxis for 26 months and who discontinued treatment by herself 1 month after the sequential infusion of two specific, third-generation anti-CD19 and anti-CD22 CAR T cell immunotherapies for refractory/relapsed diffuse large B-cell lymphoma. Remission of the primary disease was achieved after two and half months, but she was admitted with a 7-day history of vomiting, jaundice, itching and dark urine. After excluding other possible causes of acute liver damage, HBV reactivation was suspected. HBV-DNA was 4,497,000 IU/mL at that time. Following the reintroduction of entecavir, a decline in the HBV-DNA copies was observed, but ALT, AST and bilirubin were elevated, and there was no improvement of the clinical conditions. She passed away because of hepatic encephalopathy and multiple organ dysfunction syndrome 40 days after admission.

Conclusions: Our study provides the first report of the severe, early reactivation of an inactive HBsAg carrier after CAR T cell therapy in DLBCL.

Trial registration: ChiCTR-OPN-16008526.

Keywords: Chimeric antigen receptor T-cell; Diffuse large B-cell lymphoma; Hepatitis B virus; Reactivation.

Fig. 1

Sequential infusion of anti-CD 19 and anti-CD22 CAR T cell therapy. a In vitro tumor-cytotoxicity effect of CART 19 and CART 22 cells at effector/target ratios of 25:1, 5:1 and 1:1. b Levels of IL-6 after CAR T cell therapy. c Levels of ferritin after CAR T cell therapy. d Dynamic white blood cell numbers and lymphocyte numbers before and after CAR T cell therapy. e Copies of lentivirus-containing CARs in the peripheral blood after CAR T cell therapy. f CAR T cell and B cell numbers after CAR T cell therapy. g The ratio of CD4+/CD8+ T cells in the peripheral blood after CAR T cell therapy

Fig. 2

Longitudinal evaluation of hepatitis B virus (HBV)–DNA, liver enzymes, and bilirubin. a The dynamic changes in ALT, AST and total bilirubin before and after CAR T cell therapy. b HBV-DNA copies before and after CAR T cell therapy