Dept. of Medicine - Division of Hematology/Oncology, UMass Memorial Medical Center, UMass Chan Medical School, Worcester, MA, United States.
Dept. of Medicine - Division of Hematology/Oncology, UMass Memorial Medical Center, UMass Chan Medical School, Worcester, MA, United States; Center for Clinical & Translational Science, UMass Chan Medical School, Worcester, MA, United States; Cancer Biology Program, Morningside Graduate School of Biomedical Sciences, UMass Chan Medical School, Worcester, MA, United States.
Leuk Res. 2024 Jul;142:107519. doi: 10.1016/j.leukres.2024.107519. Epub 2024 May 11.
Although follicular lymphoma (FL) is traditionally classified as an indolent subtype of B cell non-Hodgkin lymphoma, clinical trajectories are often diverse based on unique disease biology, and many patients will eventually experience relapse of their disease. Furthermore, progression of disease within 24 months is associated with increased mortality rates for FL. In the last five years, we have witnessed an upsurge in the commercial availability of targeted therapies for relapsed/refractory (R/R) FL, including chimeric antigen receptor-T (CAR-T) products, bispecific T cell engagers (BiTEs), epigenetic modifier therapies, and next-generation Bruton tyrosine kinase (BTK) inhibitors. Furthermore, clinical trial options have increased tremendously and now include combinatorial strategies that exert synergy against malignant germinal center B cells. Here, we provide a 2024 update of novel therapeutic agents whose development has been informed by recent advances in the genetics and immunobiology of R/R FL. Specifically, we emphasize high-value targeted therapeutics, including anti-CD3 x anti-CD20 BiTEs and adoptive T cell therapies. We discuss prospects on selection and sequencing of BiTEs and CAR-T therapies for patients with R/R FL. We underscore the principles of FL pathobiology that are paving way for future drug discovery and shed insight into therapeutic targeting within nodal basins based on our increasing understanding of the FL microenvironment. Finally, we summarize how a greater knowledge of FL immunobiology can inform risk stratification and therapy selection on a personalized basis for R/R FL in 2025.
尽管滤泡性淋巴瘤 (FL) 传统上被归类为 B 细胞非霍奇金淋巴瘤的惰性亚型,但基于独特的疾病生物学,临床轨迹通常多种多样,许多患者最终会经历疾病复发。此外,24 个月内疾病进展与 FL 死亡率增加相关。在过去的五年中,我们见证了针对复发/难治性 (R/R) FL 的靶向治疗药物的商业可用性激增,包括嵌合抗原受体-T (CAR-T) 产品、双特异性 T 细胞衔接器 (BiTE)、表观遗传修饰疗法和下一代布鲁顿酪氨酸激酶 (BTK) 抑制剂。此外,临床试验选项大大增加,现在包括针对恶性生发中心 B 细胞发挥协同作用的组合策略。在这里,我们提供了 2024 年的新型治疗药物更新,这些药物的开发是基于 R/R FL 的遗传学和免疫生物学的最新进展。具体来说,我们强调高价值的靶向治疗药物,包括抗 CD3 x 抗 CD20 BiTE 和过继性 T 细胞疗法。我们讨论了 R/R FL 患者 BiTE 和 CAR-T 治疗的选择和排序前景。我们强调了 FL 病理生物学的原则,为未来的药物发现铺平了道路,并根据我们对 FL 微环境的理解,深入了解基于淋巴结盆地的治疗靶向。最后,我们总结了对 FL 免疫生物学的更多了解如何为 2025 年 R/R FL 的个性化风险分层和治疗选择提供信息。
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