Comparative Analysis of Bispecific Antibodies and CAR T-Cell Therapy in Follicular Lymphoma

Eur J Haematol. 2025 Jan;114(1):4-16. doi: 10.1111/ejh.14335. Epub 2024 Oct 27.

Abstract

The treatment landscape for relapsed/refractory follicular lymphoma (RR-FL) is marked by a pivotal debate between chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAbs). While both CAR-T therapy and BsAbs target similar immunobiology and molecular markers, their efficacy comparisons are hindered by the lack of direct clinical trial comparisons. Key trials, such as the ZUMA-5 study, underscore axicabtagene ciloleucel (axi-cel)'s efficacy in treating RR-FL, achieving a 79% complete response rate with a median duration of response exceeding 3 years. Similarly, lisocabtagene maraleucel (liso-cel) in the TRANSCEND FL study reports a 94% complete response rate, emphasizing robust outcomes in heavily pretreated patients. Among BsAbs, mosunetuzumab showed promise in the GO29781 trial, with a 62% overall response rate in heavily pretreated RR-FL patients. Thus, CAR-T therapy offers potential curative benefits with a single infusion. However, its efficacy is tempered by significant adverse events such as cytokine release syndrome (CRS), neurotoxicity, and cytopenias, requiring specialized management and patient monitoring. In contrast, BsAbs provide a more tolerable treatment option counterbalancing by lower response rates and frequent dosing requirements. Personalized treatment strategies are crucial because of these distinct efficacy and safety profiles. When considering cost-effectiveness, both therapies need to be evaluated in the context of their clinical outcomes and quality of life improvements. Cost-effectiveness considerations are essential; while CAR-T therapies incur higher initial costs, their potential for long-term remission may mitigate expenses associated with repeated treatments or hospitalizations. Future research into resistance mechanisms and optimal therapeutic sequencing will further refine RR-FL management strategies.

Keywords: BsAbs; CAR‐T; cost‐effectiveness; follicular lymphoma.

Publication types

  • Review
  • Comparative Study

MeSH terms

  • Antibodies, Bispecific* / therapeutic use
  • Antineoplastic Agents, Immunological / therapeutic use
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Disease Management
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Immunotherapy, Adoptive* / methods
  • Lymphoma, Follicular* / immunology
  • Lymphoma, Follicular* / therapy
  • Receptors, Chimeric Antigen / immunology
  • Treatment Outcome

Substances

  • Antibodies, Bispecific
  • Receptors, Chimeric Antigen
  • Antineoplastic Agents, Immunological