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

BackgroundHepatitis 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 presentationWe 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.ConclusionsOur study provides the first report of the severe, early reactivation of an inactive HBsAg carrier after CAR T cell therapy in DLBCL.Trial registrationChiCTR-OPN-16008526.

SARS-CoV-2 infection in immunocompromised patients: humoral versus cell-mediated immunity

“…This small case study has several important clinical implications: first, together with our previous report of fatal HBV reactivation and clearance failure post anti-CD19/22 CAR T-cell therapy, 23 we confirmed that the absence of humoral immunity can lead to a fatal virus clearance failure and aberrant T-cell activation. As the global COVID-19 pandemic continues, any decision to proceed with immunotherapy such as CAR T-cell therapy or anti-CD20-targeted therapy will require extensive discussion around the potential risks and benefits.…”

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

“…These results indicate that CAR-T cells can safely and effectively be used to treat patients who were HBV-infected under the protection of anti-HBV drugs, even patients who were HBsAg positive. Wei J et al 37 reported that a patient who had HBsAg-positive DLBCL died of HBV reactivation during CAR-T cell therapy because the patient discontinued antiviral drugs, suggesting the importance of concomitant antiviral and CAR-T cell therapy in patients with cancer who were HBV-infected.…”

Dual specific CD19/CD22‑targeted chimeric antigen receptor T‑cell therapy for refractory diffuse large B‑cell lymphoma: A case report

“…The Stanford University School of Medicine and the National Cancer Institute have launched a phase I clinical trial of anti-CD22 CAR T-cell therapy in patients with relapsed B-cell ALL and obtained significant progress. This includes CD-22 CAR that can mediate similar potent antineoplastic effects as CD19, while the dual CD19/CD22 targeted immunotherapeutic plays an important role to overcome the resistance to immunotherapy via antigen loss (41). In November 2019, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology (Wuhan, China) published a single case report of HBV reactivation after sequential treatment with CD19 and CD22 in a patient with DLBCL; after 2.5 months of CAR T-cell treatment, the tumor condition remained stable and superficial lymph nodes could not be detected (42).…”