Russler-Germain David A, Bartlett Nancy L
Division of Oncology, Washington University School of Medicine, Siteman Cancer Center, St Louis, MO.
Hematology Am Soc Hematol Educ Program. 2024 Dec 6;2024(1):310-317. doi: 10.1182/hematology.2024000667.
Treatment for relapsed/refractory (R/R) follicular lymphoma (FL) has evolved over recent years with the introduction of multiple novel immunotherapies: anti-CD3 × CD20 bispecific antibody (BsAb) T-cell engagers and anti-CD19 chimeric antigen receptor T cells (CAR T). Both drug classes are highly active, and their adverse event profiles overlap considerably, with cytokine release syndrome, cytopenias, and infections being most common. However, key differences include accessibility and logistical considerations as well as distinct neurologic toxicities, which make recommending a BsAb or CAR T a nuanced decision for each patient with R/R FL. Notably, patients could receive both classes of therapies in sequence; however, data guiding this decision are sparse. Considering the 3 most advanced agents in each class, we generally favor BsAbs before CAR T as the standard-of-care third-line treatment for the typical patient with R/R FL without concern for aggressive histologic transformation (HT). This is based on a 3-year follow-up of the mosunetuzumab phase 2 trial in R/R FL highlighting durable complete responses after a time-limited therapy with an acceptable safety profile for patients of all ages and reasonable performance status. We generally prioritize CAR T before BsAbs for patients with proven or suspected HT given the curative-potential of this approach based on trial data from R/R diffuse large B-cell lymphoma; it is unknown whether BsAbs offer the same long-term benefit in transformed FL. Overall, with the ability to personalize the sequencing of BsAbs and CAR T, the recently expanding portfolio of highly effective immunotherapies for R/R FL is poised to offer considerable benefit to this patient population.
近年来，随着多种新型免疫疗法的引入，复发/难治性（R/R）滤泡性淋巴瘤（FL）的治疗方法不断发展：抗CD3×CD20双特异性抗体（BsAb）T细胞衔接器和抗CD19嵌合抗原受体T细胞（CAR T）。这两类药物都具有很高的活性，它们的不良事件谱有相当大的重叠，细胞因子释放综合征、血细胞减少和感染最为常见。然而，关键差异包括可及性和后勤考虑因素以及不同的神经毒性，这使得为每位R/R FL患者推荐BsAb或CAR T成为一个微妙的决定。值得注意的是，患者可以依次接受这两类疗法；然而，指导这一决定的数据很少。考虑到每类中3种最先进的药物，对于没有侵袭性组织学转化（HT）的典型R/R FL患者，我们一般倾向于在CAR T之前使用BsAb作为标准的三线治疗。这是基于对R/R FL患者进行的mosunetuzumab 2期试验的3年随访，该试验强调了限时治疗后持久的完全缓解，对所有年龄和合理身体状况的患者都具有可接受的安全性。对于已证实或怀疑有HT的患者，鉴于基于R/R弥漫性大B细胞淋巴瘤试验数据的这种方法具有治愈潜力，我们一般优先考虑CAR T而不是BsAb；在转化型FL中BsAb是否能提供同样的长期益处尚不清楚。总体而言，随着能够对BsAb和CAR T的顺序进行个性化，最近为R/R FL扩展的高效免疫疗法组合有望为这一患者群体带来相当大的益处。
