Abstract
The immunogenicity of routine vaccines after B cell targeting chimeric antigen receptor T cell therapies (CARTx) is largely unknown beyond SARS-CoV-2 vaccines.
We prospectively enrolled patients who received CARTx for B cell malignancies at Fred Hutch Cancer Center and Seattle Children's Hospital from 2019-2024. Individuals in remission without treatment for persistent disease or relapse were eligible. We obtained blood pre- and post-clinically administered vaccinations. We measured IgG titers for 12 pathogens as relevant to administered vaccines, along with pre-vaccination immunoglobulin levels and B and T cell subsets. Samples obtained within eight weeks from immunoglobulin replacement therapy were excluded. We describe pre-vaccine immune reconstitution and changes in pathogen-specific IgG titers, stratified by receipt of CD19/20 versus BCMA-CARTx.
Among 87 patients enrolled, 70 (80%) received CD19/20-CARTx and 17 (20%) received BCMA-CARTx with a median age of 60 years (range, 15-81). First vaccination occurred a median of 8.6 months (IQR 6.9-14.5) after CARTx. Participants received a median of 5 unique vaccinations (IQR, 4-6) targeting 6 pathogens (IQR, 5-8), with a median of 2 doses (IQR 1-3) per vaccine. Prior to vaccination, IgA, IgG, IgM, and CD4+ T cell counts were similar in BCMA-CARTx recipients compared to CD19/20-CARTx recipients, whereas CD19+ B cell percentages were significantly higher in BCMA-CARTx recipient (Fig. 1). Most pre-vaccine pathogen-specific IgG levels were quantitatively lower in BCMA-CARTx recipients (Fig. 2), although the proportion of patients with seroprotective titers were similar (Fig. 3). Post-vaccination, 47/83 (57%) CARTx recipients had a ≥2-fold increase in pathogen-specific IgG titers for at least one pathogen. Notably, most BCMA-CARTx recipients had an increase in IgG levels after the first vaccine dose, whereas CD19/20-CARTx recipients often required >2 vaccines before titers increased (Fig 3.). Among CARTx recipients with initially non-seroprotective IgG titers, <50% seroconverted for hepatitis A and B virus, mumps, H. influenzae, C. diphtheriae and S. pneumoniae, despite >4 vaccine doses in some. Frequency of seroconversion for at least one pathogen was approximately twice as high among BCMA-CARTx recipients (8/12, 67%) compared to CD19/20-CARTx recipients (18/54, 33%).
In this cohort of CARTx recipients initiating routine vaccines after treatment, BCMA-CARTx recipients were twice as likely to seroconvert compared to CD19/20-CARTx recipients. Two or more doses of vaccines were typically required to boost pathogen-specific IgG in CD19/20-CARTx recipients. The main immunologic difference was higher pre-vaccination CD19+ B cell percentages in the BCMA-CARTx cohort, and an analysis of predictors of immunogenicity is ongoing.