Humanized anti‐CD19 chimeric antigen receptor‐T cell therapy is safe and effective in lymphoma and leukemia patients with chronic and resolved hepatitis B virus infection

Abstract

Chimeric antigen receptor‐T (CAR‐T) cell therapy is a promising treatment for CD19+ B‐cell malignancies. However, elimination of B cells by anti‐CD19 CAR‐T cells may lead to the reactivation of hepatitis B virus (HBV) and related hepatitis in patients with HBV infection. This study aims to evaluate the safety and efficacy of humanized anti‐CD19 CAR‐T (hCAR‐T) therapy in B‐cell malignancies with HBV infection. Twenty relapsed/refractory (r/r) diffuse large B‐cell lymphoma (DLBCL) and acute lymphoblastic leukemia (ALL) patients with HBV infection were treated with hCAR‐T therapy. Among them, five hepatitis B antigen‐positive patients who received antiviral prophylaxis did not develop HBV reactivation, including two patients who received both hCAR‐T and allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Among 15 patients with resolved HBV infection, two received antiviral prophylaxis, and the other 13 did not experience HBV reactivation without antiviral prophylaxis. One patient with resolved HBV infection experienced HBV reactivation 6 months after hCAR‐T therapy and sequential allo‐HSCT. Moreover, HBV infection did not affect in vivo expansion of hCAR‐T cells or increase the risk of severe cytokine release syndrome. In conclusion, hCAR‐T therapy is safe and effective in DLBCL and ALL patients with chronic and resolved HBV infection under proper antiviral prophylaxis.

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

“…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). In two of the series, the proportion of patients with positive HBsAb was particularly high (90.9 and 85%, respectively) and some of them received prophylactic nucleotide therapy.…”

Anti‐CD19 CAR T cells administration was feasible in a child with primary hepatitis B infection

“…In the published cases, [4][5][6] patients with positive HBV DNA and HBsAg have been started on entecavir no later than at initiation of lymphodepleting chemotherapy, in line with the recommendations for HBV in hematological diseases in general. 11 The ideal time for discontinuation is not known and will depend upon the level of cytopenia and the patient's status.…”

“…3 Case studies have described safe administration of CAR T-cells to adult patients with chronic HBV receiving antiviral prophylaxis. [4][5][6] We describe the first case of acute HBV infection in a child undergoing CAR T-cell therapy.…”

“…With entecavir antiviral prophylaxis, chronic HBV at the time of CAR T-cell infusion has been controllable in the majority of cases. [4][5][6]10 Importantly, no increase in the incidence of CRS or ICANS has been reported. 5 However, as fulminant hepatitis has been described in singular cases despite continuous prophylaxis, 10 regular monitoring of viral load and liver parameters is required.…”

“…[4][5][6]10 Importantly, no increase in the incidence of CRS or ICANS has been reported. 5 However, as fulminant hepatitis has been described in singular cases despite continuous prophylaxis, 10 regular monitoring of viral load and liver parameters is required.…”