Journal: Nature communications
This prospective study followed 128 patients with hematologic malignancies receiving CAR T-cell therapy targeting CD19, CD20, or BCMA to define how humoral immunity and vaccine responses behave over the first year post-treatment.
Key points:
- Pathogen-specific antibody monitoring: Pathogen-specific antibody levels against 12 vaccine-preventable infections, along with broader antibody profiles, were measured before and serially after CAR T-cell therapy, up to 12 months.
- Preservation of humoral immunity: Overall, existing pathogen-specific humoral immunity was largely preserved after CAR T-cell therapy, regardless of whether the target was CD19, CD20 (B cells), or BCMA (plasma cells). There was no major global decline in pathogen-specific antibody titers attributable to CAR T.
- Gaps in seroprotection: Despite this relative stability, a substantial proportion of patients lacked seroprotective antibody levels:
- CD19/CD20-directed therapy: By 1 year, up to about one-third of routinely vaccine-preventable pathogens lacked protective titers in recipients of CD19- and CD20-directed therapy.
- BCMA-directed therapy: In BCMA-directed recipients, nearly half of vaccine-preventable pathogens lacked protective titers at 1 year.
- Vaccine responsiveness: In a subset of 72 participants who received vaccinations after CAR T-cell therapy, the ability to mount vaccine responses varied. The strongest predictor of vaccine responsiveness was the B-cell count before vaccination.
Clinical implications:
- Residual vulnerability: CAR T-cell therapy does not uniformly erase pathogen-specific humoral immunity, but many patients remain underprotected against common vaccine-preventable infections.
- Role of B cells: Recovery or preservation of B cells is critical for effective revaccination.
- Guided revaccination strategies: These findings support systematic assessment of antibody titers and timed revaccination strategies guided by B-cell reconstitution after CAR T-cell therapy.