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Published on: February 17, 2022
SARS-CoV-2 vaccine response in CAR T-cell therapy recipients: A systematic review and preliminary observations
Muhammad Abbas Abid1, Muhammad Bilal Abid2,3
1Department of Pathology & Laboratory Medicine, Aga Khan University, Karachi, Pakistan.
Abstract:
Evolving data suggest that SARS-CoV-2 vaccine responses are blunted in allogeneic hematopoeitic cell transplant (HCT) recipients. Responses to the vaccine in chimeric antigen receptor T-cell (CAR-T) therapy are unknown and are likely to be even more diminished. We manually searched vital databases and identified 5 studies that have so far reported COVID-19 vaccine response in a total of 70 CAR-T recipients. The cumulative humoral response rate across all 5 studies was 31%. However, the results are not generalizable due to non-standardized units of humoral response measurement and a lack of external validation. Heterogeneity existed in studies regarding the timing of vaccination post-CAR-T, intervals between the vaccine doses, platforms of response assessment, vaccine platforms, and pre-vaccine immune status. CAR-T-related factors that independently impact vaccine response to prevent COVID-19 have further been reviewed. We conclude that the results must be interpreted with caution given the limitations of small sample sizes, differences in immunoassays, lack of standard definitions and clinical correlates of SARS-CoV-2 immune response, and lack of cellular responses. Until large-scale, homogenous prospective data become available, these preliminary observations will help transplant and infectious disease clinicians with their decision-making while providing care to this profoundly immunosuppressed cohort of patients.
Insights
COVID-19 vaccine responses in chimeric antigen receptor T-cell (CAR-T) therapy patients are poorly understood. A review of 5 studies found a 31% humoral response rate, but results require cautious interpretation due to study limitations.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- Allogeneic hematopoietic cell transplant (HCT) recipients exhibit blunted SARS-CoV-2 vaccine responses.
- The impact of COVID-19 vaccines on chimeric antigen receptor T-cell (CAR-T) therapy recipients remains largely unknown.
- CAR-T therapy represents a unique state of profound immunosuppression, potentially affecting vaccine efficacy.
Discussion:
- Significant heterogeneity exists across studies regarding vaccination timing, intervals, response assessment platforms, vaccine types, and pre-vaccine immune status.
- Non-standardized humoral response measurements and lack of external validation limit generalizability.
- CAR-T-related factors influencing vaccine response require further investigation.
Key Insights:
- The available data suggest a low humoral response rate to COVID-19 vaccines in CAR-T recipients.
- Limitations include small sample sizes, varied immunoassays, and absence of standardized definitions and clinical correlates for immune response.
- Cellular immune responses have not been adequately assessed.
Outlook:
- Preliminary findings necessitate cautious interpretation due to study limitations.
- Large-scale, homogenous prospective studies are crucial for definitive conclusions.
- These initial observations can guide clinicians in managing this profoundly immunosuppressed patient cohort.

