Abstract
As chimeric antigen receptor T cell therapy (CARTx) becomes a more widespread treatment for cancer and other diseases, it is important to understand pathogen-specific and non-specific immune reconstitution to guide supportive care practices. We aimed to establish and compare changes in humoral immunity before and up to one year after CD19/20- and B cell maturation (BCMA)-targeted CARTx.
In this prospective cohort study, we enrolled individuals with planned CARTx for a B cell malignancy from 5/2019-3/2023 at Fred Hutch Cancer Center or Seattle Children's Hospital. We collected blood pre-CARTx, then at 6-months and 1-year post-CARTx among those surviving ≥6 months post-CARTx without receipt of hematopoietic cell transplant or additional anti-tumor therapy for relapse. Samples were tested for IgG for 12 vaccine preventable infections; total IgG, IgA, and IgM; and B and T cell subsets. Samples collected within 8 weeks after receipt of intravenous immunoglobulin G (IVIG) were excluded. Participants with a pre-CARTx sample and ≥1 post-CARTx sample were eligible for analysis. The primary outcome was the proportion of pathogens with seroprotective IgG levels and compared by CARTx target and time point using generalized estimating equations logistic regression.
Of 279 enrolled participants, 128 (100 with CD19/20-CARTx, 28 with BCMA-CARTx) were eligible for analysis; median age was 62 years (range, 18-83 years). Pre-CARTx, most pathogen-specific median IgG levels were lower among BCMA- versus CD19/20-CARTx recipients (Fig. 1). Post-CARTx, pathogen-specific IgG remained stable among CD19/20-CARTx recipients, while BCMA-CARTx recipients had an increase in levels for most pathogens (Fig. 1). Aggregate summaries of seroprotective classifications showed similar patterns. At each time point, the proportion of pathogens with seroprotective IgG levels was significantly lower among those receiving BCMA-CARTx (42%-53%) versus CD19/20-CARTx (67%-70%) (Fig. 2A,C). Change in the proportion of pathogens with seroprotective IgG levels from pre- to post-CARTx was minimal among CD19/20-CARTx recipients, whereas BCMA-CARTx recipients had a significant increase of 11% at 1 year (95% confidence interval 0.5%-22.1%, p=0.04) (Fig. 2B,C). Most participants had below normal levels of total IgA, IgM, and IgG with additional decrements after CARTx (Fig. 3). CD19+ B cell counts were lowest among CD19/20-CARTx recipients with declining values post-CARTx, whereas BCMA-CARTx recipients showed CD19+ B cell count recovery.
In this cohort of CARTx recipients, participants receiving BCMA-CARTx had greater immune deficits than CD19/20-CARTx recipients before and up to 1 year after CARTx, though they showed recovery of humoral immunity from pre- to 1-year post-CARTx. Pathogen-specific deficits were common in both groups, underscoring the need for re-vaccination.