Journal Article (Review Article)

DKFZ-2025-01510

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Allogeneic CAR-engineered cellular therapy for relapsed and refractory large B cell lymphoma: a systematic review and meta-analysis.

Biederstädt, A. ; Bassermann, F.DKFZ* ; Hecker, J. S.

2025
Frontiers Media Lausanne

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Please use a persistent id in citations: doi:10.3389/fimmu.2025.1585556

Abstract: Relapsed/refractory (r/r) large B-cell lymphoma (LBCL) remains a difficult-to-treat disease with limited treatment options and high unmet clinical need, necessitating the development of new therapies with greater potency and broader applicability. While autologous chimeric antigen receptor (CAR)-T cell therapies have transformed the treatment landscape, 60-65% of patients receiving these therapies eventually relapse, underscoring the need for improved approaches. Allogeneic CAR-T and CAR-NK cell therapies have recently emerged as promising alternatives, offering the potential to shorten manufacturing times, reduce costs, and expand access to a broader patient population. This systematic review and meta-analysis compiles the currently available clinical trial data on the efficacy and safety of these novel therapies in adult patients with r/r LBCL.A systematic search of MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials was conducted for studies published up to January 12, 2025, involving allogeneic CAR-T and CAR-NK cell therapies in R/R LBCL. The primary outcomes assessed were the best overall response rate (bORR) and best complete response rate (bCRR) at any time point. Secondary outcomes included rates of grade 1-2 and grade 3+ cytokine release syndrome (CRS), grade 1-2 and grade 3+ immune effector cell-associated neurotoxicity syndrome (ICANS), grade 1-2 and grade 3+ infections and incidence of graft-versus-host disease (GvHD).Nineteen studies met the inclusion and exclusion criteria, encompassing 334 patients (155 CAR-NK; 179 CAR-T) evaluable for safety and 235 patients evaluable for response (77 CAR-NK; 158 CAR-T). The pooled estimates for the best overall response rate (bORR) and the best complete response rate (bCRR) were 52.5% [95% CI, 41.0-63.9] and 32.8% [95% CI, 24.2-42.0], respectively. Safety analysis revealed very low incidences of grade 3+ CRS (0.04% [95% CI 0.00-0.49]) or grade 3+ ICANS (0.64% [95% CI 0.01-2.23]) and only one occurrence of a GvH-like reaction across 334 infused patients enrolled in the included studies, highlighting the remarkable safety profile of CAR-engineered 'off-the-shelf' allogeneic approaches. The estimated overall incidence of low-grade CRS was 30% [95% CI, 14-48], while the estimated overall incidence of low-grade ICANS was 1% [95% CI, 0%-4%], markedly lower than current-generation autologous CAR-T cell products. The incidence of low-grade and severe infections was 25% [95% CI 14-36%) (n=252) and 7% [95% CI 2-14%] (n=291), respectively.Together, allogeneic CAR-T and CAR-NK cell therapies demonstrate encouraging efficacy in heavily pretreated patients with r/r LBCL. Coupled with their favorable safety profiles and the potential for off-the-shelf availability, allogeneic cell therapies hold great promise to broaden the reach of live cell-based treatments, delivering impactful results to a wider patient population in the coming years.

Keyword(s): Humans (MeSH) ; Immunotherapy, Adoptive: methods (MeSH) ; Immunotherapy, Adoptive: adverse effects (MeSH) ; Receptors, Chimeric Antigen: immunology (MeSH) ; Receptors, Chimeric Antigen: genetics (MeSH) ; Lymphoma, Large B-Cell, Diffuse: therapy (MeSH) ; Lymphoma, Large B-Cell, Diffuse: immunology (MeSH) ; Treatment Outcome (MeSH) ; Neoplasm Recurrence, Local: therapy (MeSH) ; Killer Cells, Natural: immunology (MeSH) ; Killer Cells, Natural: transplantation (MeSH) ; Transplantation, Homologous (MeSH) ; CRISPR gene editing ; adoptive cell therapy (ACT) ; allogeneic CAR-NK cells ; allogeneic CAR-T cells ; cellular engineering ; clinical trial ; large B cell lymphoma ; precision gene editing ; Receptors, Chimeric Antigen

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Contributing Institute(s):

1. DKTK Koordinierungsstelle München (MU01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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