Managing hypogammaglobulinemia in patients treated with CAR-T-cell therapy: key points for clinicians

Kampouri, Eleftheria; Walti, Carla S; Gauthier, Jordan; Hill, Joshua A.

doi:10.1080/17474086.2022.2063833

Cited by 38 publications

(35 citation statements)

References 97 publications

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“…Besides the quantitative effect on IgG level, CAR T-cells against different targets also result in different impacts on the diversity of IgG. Patients with RR multiple myeloma who were treated with BCMA-targeted CAR T-cells also lost the diversity of immunoglobulin against microorganism [74]. These patients can have prolonged and profound hypogammaglobulinemia due to the depletion of all subsets of plasma cell populations.…”

Section: Hematologic and Immune Recovery After Car T-cell Therapymentioning

confidence: 99%

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

Wudhikarn

Perales

2022

Bone Marrow Transplant

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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.

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Section: Hematologic and Immune Recovery After Car T-cell Therapymentioning

confidence: 99%

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

Wudhikarn

Perales

2022

Bone Marrow Transplant

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“…We do not expect ADA to be a limitation for CD19 TransJoin as <1% of patients treated with blinatumomab develop ADA ( 2 ), likely because it depletes B cells required for neo-antibody production. We expect some patients treated with CD19 TransJoin to require restoration of their humoral immunity with monthly infusions of intravenous immune globulin, as is the case for those treated with CD19-directed CAR-T therapy ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

Leveraging gene therapy to achieve long-term continuous or controllable expression of biotherapeutics

et al. 2022

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T cells redirected to cancer cells either via a chimeric antigen receptor (CAR-T) or a bispecific molecule have been breakthrough technologies; however, CAR-T cells require individualized manufacturing and bispecifics generally require continuous infusions. We created an off-the-shelf, single-dose solution for achieving prolonged systemic serum levels of protein immunotherapeutics via adeno-associated virus (AAV) gene transfer. We demonstrate proof of principle in a CD19 + lymphoma xenograft model using a single intravenous dose of AAV expressing a secreted version of blinatumomab, which could serve as a universal alternative for CD19 CAR-T cell therapy. In addition, we created an inducible version using an exon skipping strategy and achieved repeated, on-demand expression up to at least 36 weeks after AAV injection. Our system could be considered for short-term and/or repeated expression of other transgenes of interest for noncancer applications.

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“…The specific engagement of CAR-T-cells with their targets (CD19 or BCMA) on the surface of healthy B-lineage cells, known as "on-target off-tumor effects," largely contribute to B-cell aplasia, hypogammaglobulinemia and impaired specific antibody responses. 90,91 Other mechanisms are implicated as well and humoral deficits are commonly present even prior to CAR-T-cell therapy due to the hematologic malignancy and previous treatments. [92][93][94][95] Targeting CD19 expressed on B-cells at earlier stages of differentiation including naïve and memory B-cells, leads to B-cell depletion and hypogammaglobulinemia but pathogen specific IgG levels may be partially maintained.…”

Section: Vaccine Immunogenicity After Car-t-cell Therapymentioning

confidence: 99%

COVID‐19 after hematopoietic cell transplantation and chimeric antigen receptor (CAR)‐T‐cell therapy

Kampouri,

Hill,

Dioverti

2023

Transplant Infectious Dis

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More than 3 years have passed since Coronavirus disease 2019 (COVID‐19) was declared a global pandemic, yet COVID‐19 still severely impacts immunocompromised individuals including those treated with hematopoietic cell transplantation (HCT) and chimeric antigen receptor‐T‐cell therapies who remain at high risk for severe COVID‐19 and mortality. Despite vaccination efforts, these patients have inadequate responses due to immunosuppression, which underscores the need for additional preventive approaches. The optimal timing, schedule of vaccination, and immunological correlates for protective immunity remain unknown. Antiviral therapies used early during disease can reduce mortality and severity due to COVID‐19. The combination or sequential use of antivirals could be beneficial to control replication and prevent the development of treatment‐related mutations in protracted COVID‐19. Despite conflicting data, COVID‐19 convalescent plasma remains an option in immunocompromised patients with mild‐to‐moderate disease to prevent progression. Protracted COVID‐19 has been increasingly recognized among these patients and has been implicated in intra‐host emergence of SARS‐CoV‐2 variants. Finally, novel SARS‐CoV2‐specific T‐cells and natural killer cell‐boosting (or ‐containing) products may be active against multiple variants and are promising therapies in immunocompromised patients.

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Managing hypogammaglobulinemia in patients treated with CAR-T-cell therapy: key points for clinicians

Cited by 38 publications

References 97 publications

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

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

Leveraging gene therapy to achieve long-term continuous or controllable expression of biotherapeutics

COVID‐19 after hematopoietic cell transplantation and chimeric antigen receptor (CAR)‐T‐cell therapy

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