Study Shows Immune Response After COVID-19 Vaccine in Majority of Patients Treated With CAR T-Cell Therapy

A study published in Transplantation and Cellular Therapy found that the majority of chimeric antigen receptor (CAR) T-cell therapy recipients developed a humoral immune response to vaccination against SARS-CoV-2, with patients who received more vaccine doses showing higher SARS-CoV-2 anti-spike antibody (anti-S IgG) titers.

Patients with hematological malignancies who are treated with CAR T-cell therapy are highly immunosuppressed, and impaired humoral responses to vaccination may be caused by factors such as underlying malignancy, prior therapy lines, or hypogammaglobulinemia associated with CAR T cells.

“Evolving data demonstrates that patients who receive CD19-directed or BCMA-directed CAR T-cell therapy may be at high risk for severe COVID-19 and unfavorable outcomes such as prolonged or intractable infection,” the authors wrote. “Vaccination may be an effective strategy to prevent and mitigate disease severity.”

For immunocompromised patients, a series of 3 mRNA vaccines plus a booster or a single dose of a vector-based vaccine followed by a booster is recommended. But CAR T-cell therapy recipients have been shown to have reduced humoral responses, according to the study authors. Research is lacking in this highly immunocompromised patient population, and the new study aimed to characterize the seropositivity rate and anti-S IgG titers among CAR T-cell recipients.

The seropositivity rate was determined by an anti-S assay cutoff of ≥0.8 U/mL based on a Roche assay, and the median anti-S IgG titers were analyzed.

“Although the assay cut-off does not reflect a correlate of protection, which has not been established and differs by vaccine type, host characteristics, and circulating SARS-CoV-2 variants, higher antibody levels are clearly associated with greater vaccine-induced protection against symptomatic COVID-19,” the authors noted.

A total of 50 patients with a median age of 65 years were included in the study. Most patients (88%) received CD19-directed CAR T-cell therapy for B-cell non-Hodgkin lymphoma. Most patients received 3 mRNA vaccines total, and the majority received at least 1 vaccination after receiving CAR T-cell therapy.

Of the included patients, 32 (64%) developed a positive anti-S IgG antibody response following at least 1 vaccine, and the median SARS-CoV-2 anti-S IgG titer among those responders was 138.5 U/mL (IQR, 11.6-2541.0). Receiving 3 or more vaccine doses was associated with a higher anti-S IgG versus fewer doses in individuals who had a positive antibody response after dose 2.

Patients who received 2, 3, or 4 doses had increases in median anti-S IgG titers (2.4 U/mL vs. 7.3 U/mL vs. 71.3 U/mL). This was after adjusting for time from vaccination to anti-S IgG hypogammaglobulinemia, immune effector cell-associated neurotoxicity syndrome, vaccination before or after CAR T-cell therapy, and time from vaccination to anti-S IgG.

"In our cohort, 64% of CD19-directed or BCMA-directed CAR T-cell recipients developed a positive response to SARS-CoV-2 vaccinations, although with a relatively low median titer compared to other published data using the same assay in healthy controls," the authors wrote.

Individuals who received all vaccine doses before receiving CAR T-cell therapy had a higher median anti-S IgG titer than those who received at least 1 vaccination post–CAR T-cell therapy. The median anti-S IgG titers in patients who received BCMA- and CD19-targeted therapies were similar.

While the study had a small sample size and only assessed a single anti-S IgG level, the findings support current guidelines for SARS-CoV-2 vaccination among patients treated with CAR T-cell therapy. The study also suggests that 3 initial doses followed by a fourth booster may increase antibody titer levels in patients who do show a humoral immune response. Still, there were patients who did not respond.

“It is important to note that our analysis demonstrated that 35% of participants who received three or more vaccines were unable to mount a humoral response to vaccination, highlighting that additional doses do not necessarily increase the rate of seroconversion in certain patients in this highly immunosuppressed population,” the authors wrote. “Additional studies are warranted to identify factors that predict vaccine response for CAR T-cell recipients and to clarify optimal timing of doses pre- and post-CAR T-cell therapy.”

Reference

Aleissa MM, Little JS, Davey S, et al. SARS-CoV-2 vaccine immunogenicity among chimeric antigen receptor T-cell therapy recipients. Transplant Cell Ther. Published online March 9, 2023. doi:10.1016/j.jtct.2023.03.005