Watanabe T. Emerging role of lisocabtagene maraleucel chimeric antigen receptor-T cell in nodal and gastrointestinal follicular lymphoma. World J Gastroenterol 2025; 31(45): 112336 [PMID: 41378337 DOI: 10.3748/wjg.v31.i45.112336]
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08341203
Submitted on:
December 04, 2025, 00:09
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Reader Comments:
The editorial authored by Watanabe presents a timely and clinically pertinent overview of lisocabtagene maraleucel (liso-cel) CAR-T therapy, specifically addressing nodal and gastrointestinal follicular lymphoma (GI-FL). The author skillfully amalgamates essential findings from the TRANSCEND FL trial, emphasizing the extraordinary 97% overall response rate and a 94% complete response rate, alongside a notably reduced toxicity profile where grade ≥3 cytokine release syndrome (CRS) was absent, and grade ≥3 neurotoxicity was observed in merely 3% of patients. This concentrated analysis on the unique advantages of liso-cel—particularly its defined CD4+/CD8+ composition and the feasibility of outpatient treatment—addresses a significant void in the existing literature, especially in light of the historical exclusion of GI-FL from crucial CAR-T trials. The comparative framework juxtaposing lisocabtagene maraleucel with axicabtagene ciloleucel and tisagenlecleucel provides invaluable insights for clinical decision-making.
Nevertheless, the editorial's otherwise robust examination fails to explore subtleties regarding the durability of response in high-risk subpopulations. Although the reported 12-month progression-free survival rate exceeding 85% is promising, emerging data indicate that follicular lymphoma patients with specific genomic alterations (e.g., TP53 mutations or 1p36 deletions) display varied responsiveness to CAR-T therapy. This omission is particularly salient for GI-FL, where the biological characteristics of the disease may diverge from those of nodal FL due to influences from the microenvironment.
Furthermore, the editorial rightly recognizes cost as a barrier but insufficiently emphasizes how the manufacturing logistics of Liso-Cel disproportionately hinder accessibility in advanced GI-FL cases. Unlike nodal FL, where treatment delays may be manageable, GI-FL frequently presents urgent complications necessitating swift intervention. The three-week manufacturing timeline for liso-cel—despite improvements over previous platforms—remains a challenge for these patients, a difficulty exacerbated by the absence of validated bridging strategies tailored to gastrointestinal involvement.
Looking ahead, the integration of endoscopic and molecular staging systems (e.g., Paris classification) with CAR-T therapy response biomarkers emerges as a critical research priority. Real-world studies should specifically investigate GI-FL cohorts to ascertain whether mucosal disease localization influences CAR-T trafficking or persistence. Additionally, the formulation of risk-adapted conditioning regimens could optimize the therapeutic index in patients with gastrointestinal involvement, where organ-specific toxicities remain inadequately characterized. Watanabe's appeal for multicenter collaboration should explicitly encompass these mechanistic and health-services research inquiries to propel personalized CAR-T applications across follicular lymphoma subtypes.