The discovery and development of tisagenlecleucel for the treatment of adult patients with relapsed or refractory follicular lymphoma
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Issued Date
2025-01-01
Resource Type
ISSN
17460441
eISSN
1746045X
Scopus ID
2-s2.0-105018188904
Pubmed ID
41039722
Journal Title
Expert Opinion on Drug Discovery
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SCOPUS
Bibliographic Citation
Expert Opinion on Drug Discovery (2025)
Suggested Citation
Kungwankiattichai S., Maziarz R.T. The discovery and development of tisagenlecleucel for the treatment of adult patients with relapsed or refractory follicular lymphoma. Expert Opinion on Drug Discovery (2025). doi:10.1080/17460441.2025.2567291 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/112601
Title
The discovery and development of tisagenlecleucel for the treatment of adult patients with relapsed or refractory follicular lymphoma
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Abstract
Introduction: Follicular lymphoma (FL) is an indolent yet incurable subtype of non-Hodgkin lymphoma characterized by repeated relapses and diminishing responses with each treatment line. Although front-line chemoimmunotherapy achieves high initial response rates, a subset of patients–particularly those with early relapse (POD24)–experience poor outcomes and require alternative therapies. Tisagenlecleucel (tisa-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has emerged as a promising option for relapsed or refractory (r/r) FL, offering the potential for deep and durable remissions. Areas covered: This review covers the scientific rationale, preclinical innovations, and clinical development of tisa-cel, from its origins in 2<sup>nd</sup>-generation CAR-T engineering to its pivotal trials in hematologic malignancies. It is based on a literature search using PubMed, Embase, and conference abstracts from major hematology meetings from 1987 to April 2025. The paper deta ils the ELARA trial outcomes, subsequent long-term and real-world data, and the competitive landscape of third-line therapies for r/r FL. Expert opinion: Tisa-cel has demonstrated high response rates and sustained remissions with a favorable safety profile in heavily pretreated FL, including high-risk populations such as those with POD24. While bispecific antibodies offer convenient outpatient administration, CAR-T cell therapy provides the potential for deep and durable remissions. The 4-1BB costimulatory domain used in tisa-cel and liso-cel is associated with a lower incidence of severe CRS and ICANS compared to CD28-based constructs. the field evolves, careful patient selection and head-to-head trials will be essential to refine therapeutic sequencing in r/r FL.