Morabito Fortunato, Martino Enrica Antonia, Nizzoli Maria Elena, Talami Annalisa, Pozzi Stefano, Martino Massimo, Neri Antonino, Gentile Massimo
Gruppo Amici Dell'Ematologia Foundation-GrADE, Reggio Emilia, Italy.
Hematology Unit, Department of Onco-Hematology, AO of Cosenza, Cosenza, Italy.
Eur J Haematol. 2025 Jan;114(1):4-16. doi: 10.1111/ejh.14335. Epub 2024 Oct 27.
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.
复发/难治性滤泡性淋巴瘤（RR-FL）的治疗格局因嵌合抗原受体T细胞（CAR-T）疗法和双特异性抗体（BsAbs）之间的关键争论而备受关注。虽然CAR-T疗法和BsAbs都针对相似的免疫生物学和分子标志物，但由于缺乏直接的临床试验比较，它们的疗效比较受到阻碍。关键试验，如ZUMA-5研究，强调了阿基仑赛注射液（axi-cel）治疗RR-FL的疗效，完全缓解率达到79%，中位缓解持续时间超过3年。同样，在TRANSCEND FL研究中的利妥昔单抗（liso-cel）报告的完全缓解率为94%，突出了在经过大量预处理的患者中取得的显著疗效。在BsAbs中，莫苏单抗在GO29781试验中显示出前景，在经过大量预处理的RR-FL患者中的总缓解率为62%。因此，CAR-T疗法通过单次输注提供了潜在的治愈益处。然而，其疗效受到细胞因子释放综合征（CRS）、神经毒性和血细胞减少等严重不良事件的影响，需要专门的管理和患者监测。相比之下，BsAbs提供了一种更可耐受的治疗选择，但其较低的缓解率和频繁的给药要求使其疗效有所抵消。由于这些不同的疗效和安全性特征，个性化治疗策略至关重要。在考虑成本效益时，两种疗法都需要根据其临床结果和生活质量改善情况进行评估。成本效益考量至关重要；虽然CAR-T疗法的初始成本较高，但其长期缓解的潜力可能会减轻与重复治疗或住院相关的费用。对耐药机制和最佳治疗顺序的未来研究将进一步完善RR-FL的管理策略。
