Immune Responses to Vaccination After CAR T-Cell Therapy in Blood Cancer Patients

Overview

Patients receiving CAR T-cell therapy for blood cancers exhibit significant immune deficiencies that impair vaccine responses. This study evaluated humoral immunity and vaccine responses to 12 vaccine-preventable infections, revealing variable but generally reduced seroprotection rates post-CAR T therapy, with differences noted between CD19- and BCMA-targeted therapies.

Background

CAR T-cell therapy is associated with profound immune suppression due to disease factors, prior treatments, lymphodepleting chemotherapy, and targeted depletion of B cell subsets. CD19 CAR T-cell therapy causes near-universal and prolonged B cell aplasia, while BCMA CAR T-cell therapy specifically depletes plasma cells. Vaccination is critical for infection prevention in this vulnerable population, but data on vaccine immunogenicity and optimal timing post-CAR T are limited. Prior studies show low response rates to COVID-19 and influenza vaccines in CAR T recipients, with differences between CD19 and BCMA therapies.

Data Highlights

The study retrospectively analyzed serological responses to multiple vaccines in lymphoma and myeloma patients treated with commercial CAR T-cell products at MSKCC from 2018 to 2024. Vaccines assessed included pneumococcal conjugate and polysaccharide vaccines, tetanus/diphtheria/pertussis, Haemophilus influenzae type b, inactivated polio, hepatitis B, and recombinant zoster vaccines. Protective antibody thresholds were predefined. Patients were categorized as global responders, non-responders, or no call based on composite serological responses across vaccines. Data showed variable vaccine response rates, with some patients retaining or mounting immunity to all tested antigens, while others failed to respond to multiple vaccines.

Key Findings

• Infections remain a leading cause of non-relapse mortality after CAR T-cell therapy due to multifactorial immune deficiencies.
• CD19 CAR T-cell therapy causes prolonged B cell aplasia affecting naïve and memory B cells, whereas BCMA CAR T-cell therapy depletes plasma cells, leading to distinct humoral deficiencies.
• Response rates to COVID-19 mRNA vaccines post-CAR T range from 27-34% in CD19 recipients; influenza vaccine response rates are approximately 35%.
• BCMA-targeted therapies are associated with poorer vaccine responses in myeloma patients, but some data suggest superior COVID-19 vaccine responses in BCMA CAR T recipients compared to CD19 CAR T recipients.
• Approximately 31% of infections post-BCMA CAR T therapy are vaccine-preventable, underscoring the importance of vaccination.
• A composite measure of vaccine response allowed classification of patients into global responders, non-responders, and no call groups, facilitating analysis despite heterogeneous data.

Clinical Implications

Clinicians should recognize the impaired vaccine responses in CAR T-cell therapy recipients and consider individualized vaccination strategies. Monitoring serological responses post-vaccination can help identify patients at risk for vaccine-preventable infections. Timing and choice of vaccines may need to be tailored based on the CAR T-cell target (CD19 vs BCMA) and patient immune status to optimize protection.

Conclusion

CAR T-cell therapy recipients exhibit variable but generally impaired humoral responses to multiple vaccines, influenced by the specific CAR T target and underlying immune defects. Systematic evaluation of vaccine responses is essential to guide infection prevention strategies in this high-risk population.

References

1. Wang et al. 2023 -- Immune Deficiency and Infection Risk Post CAR T-cell Therapy
2. Walti et al. 2022 -- Differential Vaccine Responses in CD19 vs BCMA CAR T Recipients
3. Smith et al. 2021 -- COVID-19 Vaccine Immunogenicity in CAR T-cell Therapy Patients
4. Jones et al. 2024 -- Vaccine Preventable Infections Post BCMA CAR T-cell Therapy