Bispecific Antibodies—A New Hope for Patients with Diffuse Large B-Cell Lymphoma
Abstract
1. Introduction
2. Pharmacodynamics of Bispecific Antibodies
3. Bispecific Antibodies Products
4. Comparison of CAR T-Cell Therapy and BsAbs
5. Advantages and Limits of Bispecific Antibodies
6. The Safety of Bispecific Antibodies
7. Conclusions and Future Developments
Author Contributions
Funding
Conflicts of Interest
References
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Drug | Study Group/Target | Patients | Follow-Up | Outcomes | Reference |
---|---|---|---|---|---|
Epcoritamab | R/R LBCL (61.1% primary refractory, 38.9% post-CAR-T) | 157 | 10.7 months | ORR, 63.1%; CR, 38.9%; DoR, 12 mo; CR DoR, NR. | [19] |
Epcoritamab + GemOx | R/R DLBCL (transplant ineligible) | 103 | 13.2 months | ORR, 85%; CR, 61%; CR DoR, 23.6 mo; OS, 21.6 mo. | [20] |
Glofitamab | R/R B-cell NHL (incl. DLBCL) | 171 | Up to 27.4 months | ORR, 53.8%; CR, 36.8%. At RP2D: ORR, 65.7%; CR, 57.1%; 84.1% CRs ongoing. | [21] |
Glofitamab | R/R DLBCL | 154 | 12 months | CR, 39%; 35% post-CAR-T; median CR, 42d; 78% CRs ongoing; PFS, 37%. | [22] |
Glofitamab + GemOx | R/R DLBCL (transplant ineligible) | 274 | 20.7 months | OS: 25.5 vs. 12.9 mo (HR 0.62). | [23] |
Blinatumomab | Post-auto-HSCT consolidation (DLBCL/FL) | 14 | 1 year | 86% CR at day 100; 50% CR at 1 year. | [24] |
Blinatumomab | R/R DLBCL (median 3 prior therapies) | 25 | NR | ORR, 43%; CR, 19%; neurotoxicity with flat dosing. | [25] |
Blinatumomab | Richter transformation (post-RCHOP non-CR) | 25 | NR | ORR, 46%; CR, 36%. | [26] |
Mosunetuzumab | R/R B-NHL (aggressive and indolent) | 197 | NR | ORR, 34.9%/66.2%; CR, 19.4%/48.5%; CR DoR > 20 mo. | [28] |
Mosunetuzumab + Polatuzumab | R/R LBCL | 59 | NR | ORR, 59.2%; CR, 45.9%; PFS, 11.4 mo; OS, 23.3 mo. | [29] |
Mosunetuzumab + Pola-CHP | First-line DLBCL | 120 | 24 months | CR: 72.5% vs. 77.3% (Pola-R-CHP); PFS: 70.8% vs. 81.8%. | [30] |
Mosunetuzumab (post-CAR-T) | R/R LBCL post-CAR-T | 30 | NR | Better when given later; ↑ CD4/CD8/activated CD8 in responders. | [31] |
Adverse Effect | Frequency/Severity | Mechanism/Notes |
---|---|---|
CRS | Common (up to 73.2%), grade ≥ 3: ~2% | Triggered by T-cell activation and cytokine cascade (IL-6, IL-1β, TNF-α); manageable with step-up dosing. |
ICANS | Rare (~1%), lower than CAR T-cell (11%) | Related to endothelial activation and blood–brain barrier disruption; cerebral edema may occur. |
Tremor | Rare, low grade (~7%) | Mild, self-limiting; less frequent than in CAR T-cell therapy. |
Aphasia | Not reported with BsAbs | Frequently seen with CAR T-cells, but absent in BsAbs-treated patients. |
Cytopenias | Common | Likely from cytokine-induced impaired hematopoiesis. |
Febrile Neutropenia | <5% | Secondary to neutropenia. |
Infections (general) | ~10% grade ≥ 3 | Due to lymphopenia, B/T-cell dysfunction, and hypogammaglobulinemia. |
COVID-19, UTI, Pneumonia | Documented in clinical trials | Immunosuppression related. |
TLS | Rare but serious | Rapid tumor breakdown → electrolyte imbalances, AKI. |
AKI | Underreported, emerging concern | Cytokine effects, TLS, or comorbidities. |
Hypogammaglobulinemia | Variable | Due to B-cell or plasma cell depletion (e.g., CD19/CD20/BCMA targets). |
T-cell Exhaustion | Associated with infection risk | From sustained immune activation. |
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Mihaila, R.G.; Todor, S.B. Bispecific Antibodies—A New Hope for Patients with Diffuse Large B-Cell Lymphoma. J. Clin. Med. 2025, 14, 5534. https://doi.org/10.3390/jcm14155534
Mihaila RG, Todor SB. Bispecific Antibodies—A New Hope for Patients with Diffuse Large B-Cell Lymphoma. Journal of Clinical Medicine. 2025; 14(15):5534. https://doi.org/10.3390/jcm14155534
Chicago/Turabian StyleMihaila, Romeo Gabriel, and Samuel B. Todor. 2025. "Bispecific Antibodies—A New Hope for Patients with Diffuse Large B-Cell Lymphoma" Journal of Clinical Medicine 14, no. 15: 5534. https://doi.org/10.3390/jcm14155534
APA StyleMihaila, R. G., & Todor, S. B. (2025). Bispecific Antibodies—A New Hope for Patients with Diffuse Large B-Cell Lymphoma. Journal of Clinical Medicine, 14(15), 5534. https://doi.org/10.3390/jcm14155534