Overview of infectious complications among CAR T-cell therapy recipients

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Overview of infectious complications among CAR T-cell therapy recipients

Chimeric antigen receptor-modified T cell therapy has revolutionized the management of hematological malignancies. In addition to impressive malignancy-related outcomes, CAR T-cell therapy has significant toxicity-related adverse events, including cytokine release syndrome, immune effector cell associated neurotoxicity syndrome, immune effector cell-associated hematotoxicity, and opportunistic infections. Different CAR T-cell targets have different epidemiology and risk factors for infection, and these targets result in different long-term immunodeficiency states due to their distinct on-target and off-tumor effects. These effects are exacerbated by the use of multimodal immunosuppression in the management of cytokine release syndrome and immune effector cell associated neurotoxicity syndrome. The most effective course of action for managing infectious complications involves determining screening, prophylactic, and monitoring strategies and understanding the role of immunoglobulin replacement and revaccination strategies. This involves considering the nature of prior immunomodulating therapies, underlying malignancy, the CAR T-cell target, and the development and management of related adverse events. In conclusion, we now have an increasing understanding of infection management for CAR T-cell recipients. As additional effector cells and CAR T-cell targets become available, infection management strategies will continue to evolve.

One Introduction

The chimeric antigen receptor-modified T cell therapy field has rapidly expanded since the United States Food and Drug Administration first approved CD19-targeted CAR T-cells for patients with relapsed refractory B lymphoid malignancies in twenty seventeen. There are six United States Food and Drug Administration-approved CAR-T products (four CD19 CAR T-cell products and two B cell maturation CAR T-cells) for hematological malignancies; several are under investigation for other malignancies.

Clinical trials have demonstrated encouraging outcomes regarding hematological malignancy-related outcomes, albeit accompanied by infectious complications and toxicity-related adverse events. The burden of infection among CAR T-cell therapy recipients remains a critical consideration in managing these patients. Most patients are at high infection risk due to their underlying malignancies, prior lines of cancer-directed treatment, and pre-CAR T-cell lymphodepletion. Furthermore, the intensive lymphodepleting chemotherapy given before CAR-T infusion exacerbates immune system suppression, heightening susceptibility to opportunistic infections. Post infusion, immune dysregulation can lead to cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and hemophagocytic lymphohistiocytosis-like syndrome; their treatments further predispose to infection. The post-CAR T-cell period is marked by varying degrees of lymphopenia, B-cell depletion, and hypogammaglobulinemia, which may influence long-term susceptibility to infection.

Prophylactic and monitoring measures based on an understanding of infection epidemiology are part of the efforts to lessen the burden of infections among CAR-T recipients. Due to the absence of comprehensive data, prophylactic and management strategies are based on consensus guidelines largely extrapolated from the post-hematopoietic stem cell transplant population, and approaches vary widely by institution. This review aims to comprehensively analyze the epidemiology and risk factors associated with infections following CAR T-cell therapy in patients with hematological malignancy. It explores strategies for managing infectious risks associated with treatment-related toxicities and offers suggestions for screening, prophylaxis, immunoglobulin replacement therapy, and vaccinations. Further research is needed in all these domains to expand our knowledge and optimize clinical practice.

Two Epidemiology of infections

Two point one Early infections: day zero to day thirty

Two point two Late infections (beyond day thirty)

Key points:

Three Factors associated with infectious risk

Three point one Pre-CAR-T risk factors

Key points:

Three point two CAR-T/Post CAR-T related risk factors

Key points:

Three point three. Multidrug-resistant organisms and antibiotic utilization

Three point four. Fungal infections and their risk factors

Three point five. Pneumocystis jirovecii pneumonia and its risk factors

Three point six Cytomegalovirus infection and its risk factors

Three point seven Herpes simplex virus and herpes zoster virus infection and its risk factors

Three point eight Human herpes virus six infection and its risk factors

Three point nine Adenovirus infections and its risk factors

Three point ten Polyomavirus (BKv) infection and its risk factors

Four. Prevention of infections

Four point one. Baseline screening pre CAR T-cell therapy

Four point two. Prophylaxis and monitoring post CAR T-Cell infusion:

Four point three. CMV monitoring, prophylaxis, and pre-emptive therapy post CAR-T infusion

Five CRS, ICANS, and fever after CAR-T infusion

Six Emergent hemophagocytic lymphohistiocytosis-like toxicities and infections

Seven Post-infusion hypogammaglobulinemia and IgRT

Eight Vaccinations for CAR T-cell recipients

Nine Future directions and knowledge gaps

Overview

The review provides a comprehensive analysis of the infectious risks associated with CAR T-cell therapy, detailing factors that contribute to these risks and management strategies that can reduce infection rates. It emphasizes the need for ongoing research to refine prophylactic and treatment guidelines for this patient population.

Key Points

1CAR T-cell therapy significantly increases the risk of infections due to underlying malignancies and prior treatments
2Early infection risk is higher compared to late periods post-treatment
3Prophylactic strategies are based largely on consensus guidelines from related patient populations
4Factors such as prior treatments, immunity levels, and specific CAR T-cell targets influence infection risk
5The document calls for further research to optimize infection management in CAR T-cell therapy recipients

Details

Authors: Swarn Arya, Zainab Shahid
Category: Health and Medicine

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