# Bispecific Antibodies Versus Chimeric Antigen Receptor T‐Cell Therapy in Relapsed/Refractory Diffuse Large B‐Cell Lymphoma: A Comparative Narrative Review of Efficacy, Safety, and Accessibility

**Authors:** Dana Sofian Abou, Husna Irfan Thalib, Fayza Akil, Samia Zuhair Sabbagh, Hala Sofian Abou, Mable Pereira, Fatma ElSayed Hassan

PMC · DOI: 10.1002/cam4.71562 · 2026-01-29

## TL;DR

This paper compares two immunotherapies for treating relapsed/refractory diffuse large B-cell lymphoma: CAR T-cell therapy and bispecific antibodies, focusing on their effectiveness, safety, and practical use.

## Contribution

The paper provides a comparative analysis of CAR T-cell therapy and bispecific antibodies in treating relapsed/refractory DLBCL, highlighting their clinical outcomes, safety, and accessibility.

## Key findings

- CAR T-cell therapy achieves durable complete response rates of 40%–60% but faces challenges with manufacturing, cost, and toxicity.
- Bispecific antibodies offer immediate availability and outpatient administration with a favorable safety profile, though long-term durability is still being studied.

## Abstract

Diffuse large B‐cell lymphoma (DLBCL) is the most common subtype of non‐Hodgkin lymphoma, and despite advances in frontline therapies such as rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone, approximately 30%–40% of patients develop relapsed or refractory (rel/ref) disease. This subgroup has historically faced poor prognoses with limited treatment options, prompting the development of novel immunotherapeutic strategies. Chimeric antigen receptor T‐cell (CAR T) therapy and bispecific antibodies (BsAbs) have emerged as transformative approaches in this setting.

This narrative review compares these therapies across multiple domains, including mechanisms of action, clinical efficacy, safety profiles, logistics, cost, and accessibility.

CAR T therapies have demonstrated durable complete response rates (40%–60%) and extended progression‐free survival (median 11–12.5 months), but they are limited by complex manufacturing, high cost, and potentially severe toxicities. In contrast, BsAbs offer immediate, off‐the‐shelf availability, with promising efficacy and a more favorable safety profile that enables outpatient administration, although long‐term durability remains under investigation.

This review provides clinicians with a comprehensive comparison to support evidence‐based treatment selection in rel/ref DLBCL.

## Linked entities

- **Chemicals:** cyclophosphamide (PubChem CID 2907), prednisone (PubChem CID 5865)
- **Diseases:** non-Hodgkin lymphoma (MONDO:0018908)

## Full-text entities

- **Genes:** FCGR1A (Fc gamma receptor Ia) [NCBI Gene 2209] {aka CD64, CD64A, FCG1, FCGR1, FCRI, FcgammaRI}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD3E (CD3 epsilon subunit of T-cell receptor complex) [NCBI Gene 916] {aka CD3epsilon, IMD18, T3E, TCRE}, CD47 (CD47 molecule) [NCBI Gene 961] {aka IAP, MER6, OA3}, CD69 (CD69 molecule) [NCBI Gene 969] {aka AIM, BL-AC/P26, CLEC2C, EA1, GP32/28, MLR-3}, CD247 (CD247 molecule) [NCBI Gene 919] {aka CD3-ZETA, CD3H, CD3Q, CD3Z, CD3ZETA, IMD25}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, TNFRSF9 (TNF receptor superfamily member 9) [NCBI Gene 3604] {aka 4-1BB, CD137, CDw137, ILA, IMD109}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, CXADRP1 (CXADR pseudogene 1) [NCBI Gene 653108] {aka CAR, CXADRP}, MUC1 (mucin 1, cell surface associated) [NCBI Gene 4582] {aka ADMCKD, ADMCKD1, ADTKD2, CA 15-3, CD227, Ca15-3}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, CD22 (CD22 molecule) [NCBI Gene 933] {aka SIGLEC-2, SIGLEC2}, KRT20 (keratin 20) [NCBI Gene 54474] {aka CD20, CK-20, CK20, K20, KRT21}, CD28 (CD28 molecule) [NCBI Gene 940] {aka IMD123, Tp44}, SPI1 (Spi-1 proto-oncogene) [NCBI Gene 6688] {aka AGM10, OF, PU.1, SFPI1, SPI-1, SPI-A}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}
- **Diseases:** hypogammaglobulinemia (MESH:D000361), B-Cell Lymphomas (MESH:D016393), hypoxia (MESH:D000860), immune (MESH:D007154), cerebral oedema (MESH:D001929), CD (MESH:D003027), neurological, gastrointestinal, as well as electrolyte disturbances (MESH:D005767), NHL (MESH:D008228), hematologic malignancies (MESH:D019337), CRS (MESH:D000080424), hypophosphatemia (MESH:D017674), lymphopenia (MESH:D008231), pneumonia (MESH:D011014), RR-FL (MESH:D008224), cardiac toxicity (MESH:D066126), Leukopenia (MESH:D007970), tremors (MESH:D014202), ALL (MESH:D054198), Fever (MESH:D005334), encephalopathy (MESH:D001927), myeloma (MESH:D009101), neutropenia (MESH:D009503), cytopenia (MESH:D006402), mucositis (MESH:D052016), Anemia (MESH:D000740), DLBCL (MESH:D016403), lymphoproliferative malignancies (MESH:D008232), confusion (MESH:D003221), skin rashes (MESH:D005076), chills (MESH:D023341), Infection (MESH:D007239), bleeding (MESH:D006470), hypotension (MESH:D007022), cytotoxicity (MESH:D064420), lymphoma (MESH:D008223), aphasia (MESH:D001037), neurotoxicities (MESH:D020258), Thrombocytopenia (MESH:D013921), B (MESH:D006509), Fatigue (MESH:D005221), convulsions (MESH:D012640), ICANS (MESH:C000722498), cancer (MESH:D009369), PN (MESH:C565820)
- **Chemicals:** blinatumomab (MESH:C510808), tocilizumab (MESH:C502936), Oncovin (MESH:D014750), Glofitamab (MESH:C000720108), rituximab (MESH:D000069283), prednisone (MESH:D011241), 18F-FDG (MESH:D019788), cel (MESH:C054688), cyclophosphamide (MESH:D003520), lenalidomide (MESH:D000077269), doxorubicin (MESH:D004317), Odronextamab (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** -1 — Mus musculus (Mouse), Hybridoma (CVCL_C7RB)

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12853145/full.md

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Source: https://tomesphere.com/paper/PMC12853145