Antibodies against vaccine-preventable infections after CAR-T cell therapy for B cell malignancies
Carla S. Walti, Elizabeth M. Krantz, Joyce Maalouf, Jim Boonyaratanakornkit, Jacob Keane-Candib, Laurel Joncas-Schronce, Terry Stevens-Ayers, Sayan Dasgupta, Justin J. Taylor, Alexandre V. Hirayama, Merav Bar, Rebecca A. Gardner, Andrew J. Cowan, Damian J. Green, Michael J. Boeckh, David G. Maloney, Cameron J. Turtle, Joshua A. Hill
Carla S. Walti, Elizabeth M. Krantz, Joyce Maalouf, Jim Boonyaratanakornkit, Jacob Keane-Candib, Laurel Joncas-Schronce, Terry Stevens-Ayers, Sayan Dasgupta, Justin J. Taylor, Alexandre V. Hirayama, Merav Bar, Rebecca A. Gardner, Andrew J. Cowan, Damian J. Green, Michael J. Boeckh, David G. Maloney, Cameron J. Turtle, Joshua A. Hill
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Clinical Research and Public Health Infectious disease Oncology

Antibodies against vaccine-preventable infections after CAR-T cell therapy for B cell malignancies

Abstract

BACKGROUND Little is known about pathogen-specific humoral immunity after chimeric antigen receptor–modified T (CAR-T) cell therapy for B cell malignancies.METHODS We conducted a prospective cross-sectional study of CD19-targeted or B cell maturation antigen–targeted (BCMA-targeted) CAR-T cell therapy recipients at least 6 months posttreatment and in remission. We measured pathogen-specific IgG against 12 vaccine-preventable infections and the number of viral and bacterial epitopes to which IgG was detected (“epitope hits”) using a serological profiling assay. The primary outcome was the proportion of participants with IgG levels above a threshold correlated with seroprotection for vaccine-preventable infections.RESULTS We enrolled 65 children and adults a median of 20 months after CD19- (n = 54) or BCMA- (n = 11) CAR-T cell therapy. Among 30 adults without IgG replacement therapy (IGRT) in the prior 16 weeks, 27 (90%) had hypogammaglobulinemia. These individuals had seroprotection to a median of 67% (IQR, 59%–73%) of tested infections. Proportions of participants with seroprotection per pathogen were comparable to population-based studies, but most individuals lacked seroprotection to specific pathogens. Compared with CD19-CAR-T cell recipients, BCMA-CAR-T cell recipients were half as likely to have seroprotection (prevalence ratio, 0.47; 95% CI, 0.18–1.25) and had fewer pathogen-specific epitope hits (mean difference, –90 epitope hits; 95% CI, –157 to –22).CONCLUSION Seroprotection for vaccine-preventable infections in adult CD19-CAR-T cell recipients was comparable to the general population. BCMA-CAR-T cell recipients had fewer pathogen-specific antibodies. Deficits in both groups support the need for vaccine and immunoglobulin replacement therapy studies.FUNDING Swiss National Science Foundation (Early Postdoc Mobility grant P2BSP3_188162), NIH/National Cancer Institute (NIH/NCI) (U01CA247548 and P01CA018029), NIH/NCI Cancer Center Support Grants (P30CA0087-48 and P30CA015704-44), American Society for Transplantation and Cellular Therapy, and Juno Therapeutics/BMS.

Authors

Carla S. Walti, Elizabeth M. Krantz, Joyce Maalouf, Jim Boonyaratanakornkit, Jacob Keane-Candib, Laurel Joncas-Schronce, Terry Stevens-Ayers, Sayan Dasgupta, Justin J. Taylor, Alexandre V. Hirayama, Merav Bar, Rebecca A. Gardner, Andrew J. Cowan, Damian J. Green, Michael J. Boeckh, David G. Maloney, Cameron J. Turtle, Joshua A. Hill

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Figure 6

Association of primary clinical variables with seroprotective antibody titers and epitope hits among 30 participants without IGRT in the previous 16 weeks.

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Association of primary clinical variables with seroprotective antibody t...
(A) Forest plot demonstrating associations of prespecified variables with prevalence of seroprotective IgG titers to vaccine-preventable infections. Values less than 1 indicate a lower prevalence of seroprotective antibody titers compared with the reference group. For example, BCMA-CAR-T cell therapy recipients had a lower prevalence of seroprotective antibody titers compared with CD19-CAR-T cell therapy recipients, although the difference did not reach statistical significance. Dots represent PR, and whiskers indicate the 95% CI derived from GEE. (B) Violin plots comparing the number of viral or bacterial epitopes recognized by IgG (epitope hits) by prespecified variables. Violins show the distribution of the data. Box plots indicate the IQR and median. Dots in the boxes indicate the mean. P values are derived from the univariate linear regression model (Supplemental Table 6). Asterisk indicates that the CAR-T cell target remained significant in a linear regression model adjusted for prior HCT, CD19+ B cell count, and IgM level (Supplemental Table 6).