Durable preservation of antiviral antibodies after CD19-directed chimeric antigen receptor T-cell immunotherapy

Hill, Joshua A.; Krantz, Elizabeth M; Hay, Kevin A.; Dasgupta, Sayan; Stevens-Ayers, Terry; Ignacio, Rachel A. Bender; Bar, Merav; Maalouf, Joyce; Cherian, Sindhu; Chen, Xueyan; Pepper, Greg; Riddell, Stanley R.; Maloney, David G.; Boeckh, Michael; Turtle, Cameron J.

doi:10.1182/bloodadvances.2019000717

Cited by 62 publications

(65 citation statements)

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“…The retained antibody repertoire could represent a core stable LLPC repertoire (~90%), and the 10% that was lost could represent a transient repertoire derived from IgG-secreting B cells and plasmablasts. This result is consistent with previous studies that showed no effect of immunosuppressive therapy, such as B celldepleting anti-CD19 or anti-CD20 treatment, on retention of the majority of the antibody repertoire (17,19,21,22). Therefore, measles is associated with greater loss of antibodymediated epitope recognition than can be explained by ablation of B cells, suggesting a direct effect on the LLPC compartment.…”

Section: Measles Modulates the Diversity Of The Antibody Repertoire Asupporting

confidence: 92%

“…Antibodies are thought to better represent long-lived humoral memory (18,20). Most antibodies in the peripheral blood are produced by bone marrow long-lived plasma cells (LLPCs) and are impervious to disruptions in peripheral memory cells (17)(18)(19)(20)(21)(22). Changes in pathogen-specific antibodies measured in the peripheral blood reflect changes in the long-lived permanent memory repertoire.…”

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confidence: 99%

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Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens

Mina

Kula

Leng

et al. 2019

Science

361

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Measles virus is directly responsible for more than 100,000 deaths yearly. Epidemiological studies have associated measles with increased morbidity and mortality for years after infection, but the reasons why are poorly understood. Measles virus infects immune cells, causing acute immune suppression. To identify and quantify long-term effects of measles on the immune system, we used VirScan, an assay that tracks antibodies to thousands of pathogen epitopes in blood. We studied 77 unvaccinated children before and 2 months after natural measles virus infection. Measles caused elimination of 11 to 73% of the antibody repertoire across individuals. Recovery of antibodies was detected after natural reexposure to pathogens. Notably, these immune system effects were not observed in infants vaccinated against MMR (measles, mumps, and rubella), but were confirmed in measles-infected macaques. The reduction in humoral immune memory after measles infection generates potential vulnerability to future infections, underscoring the need for widespread vaccination.

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Section: Measles Modulates the Diversity Of The Antibody Repertoire Asupporting

confidence: 92%

mentioning

confidence: 99%

Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens

Mina

Kula

Leng

et al. 2019

Science

361

289

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“…However, there are data showing persistent long-lived plasma cells after CAR T cell therapy 22 . In addition, Hill and colleagues recently demonstrated preserved anti-viral humoral immune response in patients treated with CD19 CAR T cells 23 . The authors reported sustained anti-measle IgG level independent of the total IgG level in 95% of patients.…”

Section: Discussionmentioning

confidence: 99%

Infection during the first year in patients treated with CD19 CAR T cells for diffuse large B cell lymphoma

et al. 2020

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CD19-targeted chimeric antigen receptor (CAR) T cell therapy is an effective treatment for diffuse large B cell lymphoma (DLBCL). In addition to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS), B cell aplasia and hypogammaglobulinemia are common toxicities predisposing these patients to infections. We analyzed 60 patients with DLBCL treated with FDA-approved CD19 CAR T cells and report the incidence, risk factors, and management of infections during the first year after treatment. A total of 101 infectious events were observed, including 25 mild, 51 moderate, 23 severe, 1 life-threatening, and 1 fatal infection. Bacteria were the most common causative pathogens. The cumulative incidence of overall, bacterial, severe bacterial, viral, and fungal infection at 1 year were 63.3%, 57.2%, 29.6%, 44.7%, and 4%, respectively. In multivariate analyses, the use of systemic corticosteroids for the management of CRS or ICANS was associated with an increased risk of infections and prolonged admission. Impaired performance status and history of infections within 30 days before CAR T cell therapy was a risk factor for severe bacterial infection. In conclusion, infections were common within the first 60 days after CAR T cell therapy, however, they were not associated with an increased risk of death.

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“…7 12 Because long-lived plasma cells are not a direct target of CD19 + CAR-T cells, the humoral immunity may be preserved. 16 In the absence of data, we recommend complete vaccinations according to the patient's age and seroprotection status.…”

Section: Icans Managementmentioning

confidence: 99%

How I treat adverse effects of CAR-T cell therapy

et al. 2020

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Chimeric antigenreceptor (CAR) T cell therapy has demonstrated efficacy in B cell malignancies, particularly for acute lymphoblastic leukaemia (ALL) and non‑Hodgkin lymphomas. However, this regimen is not harmless and, in some patients, can lead to a multi organ failure. For this reason, the knowledge and the early recognition and management of the side effects related to CAR-T cell therapy for the staff is mandatory. In this review, we have summarised the current recommendations for the identification, gradation and management of the cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as infections, and related to CAR-T cell therapy.

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Durable preservation of antiviral antibodies after CD19-directed chimeric antigen receptor T-cell immunotherapy

Abstract: Key Points Virus-specific IgG levels were stable for up to 1 year after CD19-CARTx in adults with durable complete remission. Preexisting humoral immunity may be preserved in adult recipients of CD19-CARTx.

Cited by 62 publications

References 50 publications

Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens

Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens

Infection during the first year in patients treated with CD19 CAR T cells for diffuse large B cell lymphoma

How I treat adverse effects of CAR-T cell therapy

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