Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy

Abstract

CD19-targeted chimeric antigen receptor (CAR) T-cell becomes a breakthrough therapy providing excellent remission rates and durable disease control for patients with relapsed/refractory (R/R) hematologic malignancies. However, CAR T-cells have several potential side effects including cytokine release syndrome, neurotoxicities, cytopenia, and hypogammaglobulinemia. Infection has been increasingly recognized as a complication of CAR T-cell therapy. Several factors predispose CAR T-cell recipients to infection. Fortunately, although studies show a high incidence of infection post-CAR T-cells, most infections are manageable. In contrast to patients who undergo hematopoietic stem cell transplant, less is known about post-CAR T-cell immune reconstitution. Therefore, evidence regarding antimicrobial prophylaxis and vaccination strategies in these patients is more limited. As CAR T-cell therapy becomes the standard treatment for R/R B lymphoid malignancies, we should expect a larger impact of infections in these patients and the need for increased clinical attention. Studies exploring infection and immune reconstitution after CAR T-cell therapy are clinically relevant and will provide us with a better understanding of the dynamics of immune function after CAR T-cell therapy including insights into appropriate strategies for prophylaxis and treatment of infections in these patients. In this review, we describe infections in recipients of CAR T-cells, and discuss risk factors and potential mitigation strategies.

CD19/CD22 dual-targeting Chimeric antigen receptor T cell therapy bridging to allogeneic hematopoietic stem cell transplantation for B-cell acute lymphoblastic leukemia delays platelet recovery and increases risks of cytomegalovirus and Epstein-Barr Virus viremia after transplantation

“…As a consequence, integrating CAR-T and HSCT may result in severe posttransplant hypogammaglobulinemia, which accounts for the high incidence of CMV and EBV infections. In contrast, the knowledge of immune reconstitution after CAR-T therapy remains less clear compared with HSCT (29). Low CD4 count has been documented for up to 1-year post-infusion which is correlated with signi cantly longer duration of B-cell aplasia (33).…”

“…The cell-mediated immune response and the humoral response with neutralizing antibodies play a role in conferring protective immunity against CMV and EBV infection (26, 27, 28). CAR-T recipients are highly susceptible to viral infection because of CAR-T cell-mediated immune system dysregulation (29). Viral infections have been be the most common cause of infection in febrile CAR-T recipients in some studies (30).…”

Cytopenia after chimeric antigen receptor T cell immunotherapy in relapsed or refractory lymphoma

“…Many studies have been conducted to assess infection rates in individuals receiving CAR-T-cell treatment. The incidence of early infection (<30 d) ranges from 18% to 60% ( 12 , 27 – 29 ) in prospective clinical trials and retrospective analyses. For example, Hill ( 12 ) described 23% of patients with different B lymphoid malignancies had infection during the first 28 days following CAR-T-cell infusion.…”

Clinical Strategies for Enhancing the Efficacy of CAR T-Cell Therapy for Hematological Malignancies

“…The occurrence of infection is closely related to the patient’s blood immunodeficiency. The reasons include tumor cell suppression of normal immune cells, lymphatic depletion, and subsequent systemic reactions to serious complications [ 108 ]. The mechanism of these side effects is variable and complex, and it may require a professional team devoted to management of side effects, making it an important means to promote efficacy.…”