Prognostic significance of immune reconstitution following CD19 CAR T-cell therapy for relapsed/refractory B-cell lymphoma Journal Article


Authors: Stock, S.; Bücklein, V. L.; Blumenberg, V.; Magno, G.; Emhardt, A. J.; Holzem, A. M. E.; Cordas dos Santos, D. M.; Schmidt, C.; Grießhammer, S.; Frölich, L.; Kobold, S.; von Bergwelt-Baildon, M.; Rejeski, K.; Subklewe, M.
Article Title: Prognostic significance of immune reconstitution following CD19 CAR T-cell therapy for relapsed/refractory B-cell lymphoma
Abstract: Immune deficits after CD19 chimeric antigen receptor (CAR) T-cell therapy can be long-lasting, predisposing patients to infections and non-relapse mortality. In B-cell non-Hodgkin lymphoma (B-NHL), the prognostic impact of immune reconstitution (IR) remains ill-defined, and detailed cross-product comparisons have not been performed to date. In this retrospective observational study, we longitudinally characterized lymphocyte subsets and immunoglobulin levels in 105 B-NHL patients to assess patterns of immune recovery arising after CD19 CAR-T. Three key IR criteria were defined as CD4+ T helper (TH) cells > 200/μL, any detectable B cells, and serum immunoglobulin G (IgG) levels >4 g/L. After a median follow-up of 24.6 months, 38% of patients displayed TH cells, 11% showed any B cells, and 41% had IgG recovery. Notable product-specific differences emerged, including deeper TH cell aplasia with CD28z- versus longer B-cell aplasia with 41BBz-based products. Patients with any IR recovery experienced extended progression-free survival (PFS) (median 20.8 vs. 1.7 months, p < 0.0001) and overall survival (OS) (34.9 vs. 4.0 months, p < 0.0001). While landmark analysis at 90 days confirmed improved PFS in patients with any recovery (34.9 vs. 8.6 months, p = 0.005), no significant OS difference was noted. Notably, 72% of patients with refractory disease never displayed recovery of any IR criteria. Early progressors showed diminished IR at the time of progression/relapse compared to patients with late progression/recurrence (after Day 90). Our results highlight the profound immune deficits observed after CD19 CAR-T and shed light on the intersection of IR and efficacy in B-NHL. Importantly, IR was impaired considerably postprogression, carrying significant implications for subsequent T-cell-engaging therapies and treatment sequencing. © 2025 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.
Keywords: adult; aged; major clinical study; overall survival; cancer recurrence; drug megadose; bendamustine; retrospective study; b cell lymphoma; immunoglobulin g; glucocorticoid; observational study; immunoglobulin blood level; cd19 antigen; predictive value; longitudinal study; immune reconstitution; lymphocyte subpopulation; refractory cancer; tocilizumab; human; male; female; article; tisagenlecleucel t; chimeric antigen receptor t-cell immunotherapy; axicabtagene ciloleucel; lisocabtagene maraleucel; brexucabtagene autoleucel; tisa cel; liso cel
Journal Title: HemaSphere
Volume: 9
Issue: 1
ISSN: 2572-9241
Publisher: Lippincott Williams & Wilkins  
Date Published: 2025-01-01
Start Page: e70062
Language: English
DOI: 10.1002/hem3.70062
PROVIDER: scopus
PMCID: PMC11726691
PUBMED: 39807276
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Kai Dannebom Rejeski
    24 Rejeski