Pre-treatment vaccine seroprotection is markedly lower in BCMA-CAR vs CD19-CAR recipients with limited post-therapy modulation
Year: 2025
Type: conference-abstract
Abstract: Introduction:Infections are the leading cause of non-relapse mortality in patients (pts) treated with chimeric antigen receptor T cells (CARs), accounting for more than 50% of all events. This is in part due to prolonged neutropenia, as well as protracted immune reconstitution deficits defined by B-cell aplasia, hypogammaglobulinemia, and sustained CD4+ T-cell lymphopenia. Vaccinations play a fundamental role in the prevention of infectious diseases. A consensus on the optimal post-CAR T-cell vaccination schedule is lacking, as data on the prevalence of protective vaccine titers prior to as well as their persistence after CD19- and BCMA- CAR T treatment remain limited. Aim: We analyzed the antibody titers against common vaccine-preventable infections before and after CD19 and BCMA-directed CART cell therapy. Methods:In this retrospective observational study, we included pts treated with commercial BCMA- or CD19-directed CARs at two German academic centers between 2019 and 2024. Immunoglobulin G (IgG) antibody titers against vaccine-preventable infections (mumps, measles, rubella, varicella zoster virus [VZV], hepatitis [hep] A, hep B and SARS-CoV-2) were assessed prior to CAR T-cell infusion and starting from 3 months after CAR T-cell infusion, according to sample availability. Only pts who had not progressed or received further antineoplastic therapy at timepoint of post-CARs sample collection were considered eligible. Pts treated prior to 01/2021 were excluded from the SARS-CoV-2 analysis.According to institutional guidelines, pts did not receive vaccinations against MMR-V or hepatitis following CAR T cell treatment. However, a substantial percentage of pts underwent SARS-CoV-2 vaccination. Intravenous immunoglobulins (IVIGs) were administered to pts with IgG of < 4 g/L and recurrent infections as per institutional practice. Results: Of the 124 pts included in the analysis, 91 received CD19-directed CARs (Large B-Cell Lymphoma n=77, Mantle Cell Lymphoma n=9, Acute Lymphoblastic Leukemia n=5), while 33 were treated with anti-BMCA CARs (Multiple Myeloma n=32, POEMS n=1). Median age was 63 years (range 19-83). 11/124 pts were administered IVIGs within the 8 weeks prior to titer measurement. Prior to CAR T-cell infusion, the rates of seroprotection were 56% (mumps), 77% (measles), 73% (rubella), 77% (VZV), 48% (hep A), 38% (hep B) and 80% (SARS-CoV-2) across all available pts samples (n=81). Notably, the proportion of seroprotected participants at baseline was significantly higher in lymphoma and leukemia pts compared to myeloma pts for mumps (66.2% vs 0.0%, p<0.0001), measles (88.2% vs 15.4%, p<0.0001), rubella (77.9% vs 46.2%, p=0.036), VZV (88.2% vs 0.0%, p<0.0001) and hep B (42.7% vs 8.3%, p=0.026), while no significant differences were detected concerning hep A (51.5% vs 25.0%) or SARS-CoV-2 (76.7% vs 92.3%). Following CAR T-cell treatment, sample availability amounted to 121 (CD19 n=91, BCMA n=30). Again, we observed significantly higher seroprotection rates in CD19- compared to BCMA-CAR T-cell recipients for mumps (71.4% vs 33.3%, p=0.0004), measles (91.2% vs 60.0%, p=0.0002), rubella (84.6% vs 56.7%, p=0.0043), and VZV (92.3% vs 60.0%, p=0.001). No significant differences were observed for hep A (62.6% vs 82.8%) and B (55.0% vs 65.5%) or SARS-CoV-2 (81.3% vs 92.6%). Paired pre- and post-treatment samples were available for 78 pts (68 CD19, 10 BCMA). Overall, only 1-6% of pts lost immunity after CARs compared to baseline. In a multivariable logistic regression accounting for age, IVIG replacement, CAR T-cell target and baseline seroprotection, seronegativity at baseline was the only factor significantly associated with the absence of immunity after CAR T-cell treatment to hep A, mumps, measles, rubella and VZV, while IVIG replacement showed the strongest association with anti-HBs-positivity. Conclusion: To our knowledge, this is the largest longitudinal study to date assessing vaccine-specific antibody titers in CAR T-cell recipients. We found significantly lower seroprotection rates in BCMA-CAR-T compared to CD19-CAR-T recipients, both at baseline and following therapy. The unexpectedly low antibody titers in multiple myeloma pts may reflect disease-related plasma cell dysfunction and prior treatment, including anti-CD38 antibodies. These real-world findings support the need for tailored vaccination strategies prior and post-CAR-T, with the ultimate goal of reducing infection-related non-relapse mortality.
Source: Blood
Authors: Giulia Magno, Elif Apak, Savanna Süß, Giulia Rappa, Patricia M. Späth, Sophia Stock, Alessandra Holzem, Wajma Shahbaz, Tobias Tix, Bernhard Ismann, Judith S. Hecker, Florian Bassermann, Sebastian Theurich, Michael Von Bergwelt, Kai Rejeski, Oliver T. Keppler, Marion Subklewe, Veit Buecklein
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7108630470
Cites:
Cited by:
Related to: