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Immunotherapy

Risk of HBV reactivation post CD19-CAR-T cell therapy in DLBCL patients with concomitant chronic HBV infection

Leukemia volume 34, pages 3055–3059 (2020)Cite this article

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Patients with chronic hepatitis B virus (HBV) infection have been epidemiologically confirmed to show an increased risk of developing diffuse large B-cell lymphoma (DLBCL) [1]. Recently, a direct etiologic link between HBV infection and B-cell lymphomagenesis has been unraveled from altered genetic spectrum in HBV-infected DLBCL [2]. Wang et al. [3] analyzed the biological association of HBV infection with aggressive B-cell non-Hodgkin’s lymphoma (B-NHL), and showed the prevalence of HBV infection was significantly higher in the B-NHL group than that in the general population (10.46% versus 7.2%) and also patients with other types of blood cancer. HBV reactivation has been reported from various patients who received cytotoxic chemotherapies, with variable clinical outcomes, from asymptomatic to severe including fatal hepatitis. The risk of reactivation closely depends on HBV serologic status, in which those lymphoma patients with chronic HBV infection (defined as positive hepatitis B surface antigen (HBsAg) serology) who receive rituximab-based immunochemotherapy have the highest risk of HBV reactivation per se [4].

The mechanisms underlying the reactivation in NHL are not fully clear, but include amplified viral replication, suppressed immunity, and dysregulated immune functions post cessation of anticancer therapy [4]. Anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy is an effective treatment in relapsed/refractory (R/R)-DLBCL. Several clinical trials have shown that CAR-T cell therapy achieves an overall response (OR) rate of 52–83% in patients with R/R-DLBCL [5, 6]. Importantly, long-term efficacies have been observed suggesting that anti-CD19-CAR-T cell therapy can be curative for these patients. Despite the therapeutic potency, safety profile critically impacts its clinical application. Lymphoma patients who receive CD19-CAR-T cell infusion may be significantly immunosuppressed due to conditioning chemotherapy, normal B-cell depletion, and hypogammaglobulinemia resulted from previous rituximab treatment, and therefore they are susceptible to infections [7]. Such mechanisms of immunosuppression may constitute part of revenues responsible for HBV reactivation. Recently, HBV reactivation was reported in one of three R/R-DLBCL patients with concomitant HBV or HCV infection post CD19-CAR-T (axicabtagene ciloleucel) treatment [8]. However, HBV reactivation risk and HBV-related hepatitis in HBsAg-positive DLBCL patients who underwent CD19-CAR-T cell therapy are unknown.

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Fig. 1: Longitudinal assessment of HBV-DNA, liver function, serum immunoglobulin, B-cell recovery, and overall survival (OS) of HBsAg-positive DLBCL patients who underwent CD19-CAR-T cell therapy.

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Acknowledgements

This study was supported by funds from the National Natural Science Foundation of China (No. 81830006, 81830004, 81670178), Science Technology Department of Zhejiang Province (No. 2018C03016-1), and the Natural Science Foundation of Zhejiang Province (No. LY20H080006, LY18H16008).

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  1. These authors contributed equally: Chunmei Yang, Mixue Xie

Authors and Affiliations

  1. Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China

    Chunmei Yang & Mixue Xie

  2. Institute of Hematology, Zhejiang University, Hangzhou, 310003, Zhejiang, China

    Chunmei Yang, Mixue Xie, Kaifeng Zhang & Wenbin Qian

  3. Department of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China

    Hui Liu & Wenbin Qian

  4. Department of Hematology, Tongji Hospital of Tongji University, Shanghai, 200065, China

    Aibin Liang

  5. Hematopathology Division and Department of Pathology, Duke University School of Medicine, Duke University Medical Center and Cancer Institute, Durham, NC, 27710, USA

    Ken H. Young

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Contributions

Conception, design, and manuscript writing: WQ, AL, and KHY. Collection, analysis, and interpretation: CY, MX, KZ, and HL. All authors were involved at each stage of manuscript preparation and approved the final version.

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Correspondence to Aibin Liang, Ken H. Young or Wenbin Qian.

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Yang, C., Xie, M., Zhang, K. et al. Risk of HBV reactivation post CD19-CAR-T cell therapy in DLBCL patients with concomitant chronic HBV infection. Leukemia 34, 3055–3059 (2020). https://doi.org/10.1038/s41375-020-0913-y

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