Low incidence of invasive fungal disease following CD19 chimeric antigen receptor T-cell therapy for non-Hodgkin lymphoma

Little, Joanna M.; Aleissa, Muneerah M; Beluch, Katherine; Gonzalez-Bocco, Isabel H; Marty, Francisco M.; Manne‐Goehler, Jennifer; Koo, Sophia; Hammond, Sarah P.; Jacobson, Caron A.

doi:10.1182/bloodadvances.2022007474

Cited by 39 publications

(54 citation statements)

References 58 publications

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“…The risk of cytopenias is associated with higher-grade CRS, multiple previous lines of therapy, receipt of allogeneic HSCT ≤1 year prior to CAR T cell infusion, baseline cytopenia and the presence of bone marrow malignancy 95,96 . Despite these widespread changes to the immune system, the incidence of severe infections >1 month after CAR T cell therapy is relatively low compared to the incidence of severe infections in the first month after CAR T cell infusion, and the incidence of such infections decreases with time after infusion 16,89,94,97 . However, data in this area are sparse because most studies have not focused on infections occurring many months after CAR T cell infusion 98 .…”

Section: Review Articlementioning

confidence: 99%

Long-term outcomes following CAR T cell therapy: what we know so far

2023

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Chimeric antigen receptors (CAR) are engineered fusion proteins designed to target T cells to antigens expressed on cancer cells. CAR T cells are now an established treatment for patients with relapsed and/or refractory B cell lymphomas, B cell acute lymphoblastic leukaemia and multiple myeloma. At the time of this writing, over a decade of follow-up data are available from the initial patients who received CD19-targeted CAR T cells for B cell malignancies. Data on the outcomes of patients who received B cell maturation antigen (BCMA)targeted CAR T cells for multiple myeloma are more limited owing to the more recent development of these constructs. In this Review, we summarize long-term follow-up data on efficacy and toxicities from patients treated with CAR T cells targeting CD19 or BCMA. Overall, the data demonstrate that CD19-targeted CAR T cells can induce prolonged remissions in patients with B cell malignancies, often with minimal long-term toxicities, and are probably curative for a subset of patients. By contrast, remissions induced by BCMA-targeted CAR T cells are typically more short-lived but also generally have only limited long-term toxicities. We discuss factors associated with longterm remissions, including the depth of initial response, malignancy characteristics predictive of response, peak circulating CAR levels and the role of lymphodepleting chemotherapy. We also discuss ongoing investigational strategies designed to improve the length of remission following CAR T cell therapy. Sections• Ongoing research efforts are attempting to improve the durability of responses after CAR T cell therapy, for example, through improved patient selection, novel CAR designs, including those targeting multiple antigens, and modifications to the manufacturing process.

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Section: Review Articlementioning

confidence: 99%

Long-term outcomes following CAR T cell therapy: what we know so far

2023

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“…18 Antimicrobial prophylaxis is the cornerstone of prevention of late infections after CAR-T cell therapy and is largely extrapolated from the approach to HCT recipients. Pneumocystis prophylaxis (e.g., trimethoprim/sulfamethoxazole) and herpes simplex/zoster prophylaxis (e.g., valacyclovir) are recommended for ≥6-12 months post CAR-T cell therapy and until recovery of CD4 count to >200 Â 10 6 / L. 18,19 Although fungal infections are generally rare after CAR-T cell therapy, 81 antimould prophylaxis is suggested in the setting of prolonged neutropenia. 73,82 Antibacterial prophylaxis has also been associated with reduced risks of infection among high-risk patients, 55 and may be considered for those with prolonged neutropenia in accordance with institutional policies and local resistance patterns.…”

Section: Late Infectionsmentioning

confidence: 99%

“…Of note, patients with multiple myeloma may be particularly susceptible to infection owing to the elimination of antibody‐producing plasma cells by BCMA‐directed CAR‐T cell therapy 78–80 . In addition to B‐cell aplasia, CAR‐T cell recipients commonly experience delayed T‐cell reconstitution which may increase the risk of late opportunistic infections such as pneumocystis pneumonia 73,81 . Indeed, the median CD4 count 1 year after infusion is only 155 × 10 6 /L, 52 with CD4 count remaining <200 × 10 6 /L in 62% of patients at 1 year and in 27% at 2 years 50 .…”

Section: Late Infectionsmentioning

confidence: 99%

“…[78][79][80] In addition to B-cell aplasia, CAR-T cell recipients commonly experience delayed T-cell reconstitution which may increase the risk of late opportunistic infections such as pneumocystis pneumonia. 73,81 Indeed, the median CD4 count 1 year after infusion is only 155 Â 10 6 /L, 52 with CD4 count remaining <200 Â 10 6 /L in 62% of patients at 1 year and in 27% at 2 years. 50 To monitor immune reconstitution, measurements of CD4+ T cells, B cells, and quantitative immunoglobulins should be obtained periodically during long-term follow-up.…”

Section: Late Infectionsmentioning

confidence: 99%

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Long‐term survivorship care after CAR‐T cell therapy

Puckrin,

Jamani,

Jimenez‐Zepeda

2023

European J of Haematology

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While cytokine release syndrome and immune effector cell‐associated neurotoxicity syndrome are well‐recognized acute toxicities of chimeric antigen receptor (CAR) T cell therapy, these complications have become increasingly manageable by protocolized treatment algorithms incorporating the early administration of tocilizumab and corticosteroids. As CAR‐T cell therapy expands to new disease indications and the number of long‐term survivors steadily increases, there is growing recognition of the need to appropriately evaluate and manage the late effects of CAR‐T cell therapy, including late‐onset or persistent neurotoxicity, prolonged cytopenias, delayed immune reconstitution and infections, subsequent malignancies, organ dysfunction, psychological distress, and fertility implications. In this review, we provide a practical approach to the long‐term survivorship care of the CAR‐T cell recipient, with a focus on the optimal strategies to address the common and challenging late complications affecting this unique population.

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“…The incidence of cryptococcus in HCT recipients has varied in studies from 0.6 to 2%. 57,58 Cryptococcal disease is commonly diagnosed by serum cryptococcal antigen test, direct microscopic visualization in cultures, histopathologic or cytopathologic samples. CT imaging is helpful but not specific for pulmonary cryptococcus, with single to multiple nodules, cavitation, and consolidations seen.…”

Section: Endemic Fungimentioning

confidence: 99%

Evaluation of pulmonary abnormalities in recipients of hematopoietic cell transplants and cellular therapies

Thomas,

Boatman

2023

Transplant Infectious Dis

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Hematopoietic cell transplant (HCT) and chimeric antigen receptor T‐cell (CAR‐T) therapy recipients are susceptible to multiple pulmonary complications that are caused by infectious and noninfectious processes. Numerous variables can be associated with specific pulmonary diseases including time from transplantation, presence of graft versus host disease (GVHD), underlying disease, and prolonged neutropenia and lymphocytopenia. Most pulmonary complications are infectious in origin, with bacterial pneumonia remaining the most common pulmonary infection, particularly before neutrophil engraftment. Invasive fungal infections continue to affect this patient population even when antifungal prophylaxis is used. Noninfectious pulmonary complications include a wide differential of pathologies in this population, and as clinical presentations of these various pulmonary disorders often overlap, clinicians frequently will use a multidisciplinary approach in diagnosing these abnormalities. Radiography, particularly with chest computed tomography (CT) imaging, is an essential tool in identifying pulmonary pathology and potential sources. While standard microbiological cultures of respiratory specimens are still utilized, their role is limited by low sensitivity and diagnostic yield. The likelihood of obtaining a diagnosis can be improved by using other microbiological assays, including fungal antigen tests and molecular diagnostic methods, particularly if specimens are collected via bronchoscopy. This review will highlight the more common causes of pulmonary diseases encountered after HCT and CAR‐T and will examine the different methods in their diagnosis.

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Low incidence of invasive fungal disease following CD19 chimeric antigen receptor T-cell therapy for non-Hodgkin lymphoma

Cited by 39 publications

References 58 publications

Long-term outcomes following CAR T cell therapy: what we know so far

Long-term outcomes following CAR T cell therapy: what we know so far

Long‐term survivorship care after CAR‐T cell therapy

Evaluation of pulmonary abnormalities in recipients of hematopoietic cell transplants and cellular therapies

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