Chen Chung-Jiah J, Choi Michael Y, Heyman Benjamin M
Department of Medicine, Division of Hematology-Oncology, UC San Diego Health, La Jolla, CA 92037, USA.
Department of Medicine, Division of Regenerative Medicine, UC San Diego Health, La Jolla, CA 92037, USA.
Cancers (Basel). 2023 Sep 8;15(18):4483. doi: 10.3390/cancers15184483.
BACKGROUND: The treatment of follicular lymphoma (FL) has previously centered on chemoimmunotherapy, which can be disadvantageous due to patient intolerance, cumulative toxicities, and disease refractoriness. Targeted therapies can produce deep responses and improve progression-free and overall survival with more tolerable adverse event profiles. METHODS: We summarize the current literature and key clinical trials regarding targeted therapies in follicular lymphoma both in the front-line and in the relapsed-refractory setting. RESULTS: Targeted therapies studied in FL include immune modulators, anti-CD20 antibodies, Bruton's tyrosine kinase (BTK) inhibitors, enhancers of zeste homolog 2 (EZH2) inhibitors, phosphoinositide 3-kinase (PI3K) inhibitors, and B-cell lymphoma 2 (BCL-2) inhibitors. Chimeric antigen receptor (CAR-T) therapy and bispecific T-cell engager (BiTE) therapies also show promise in monotherapy and in combination with targeted therapies. These therapies exhibit high overall response rates and substantial progression-free survival and overall survival, even in high-risk patients or patients previously refractory to chemotherapy or rituximab. Adverse events vary substantially but are generally manageable and compare favorably to the cumulative toxicities of chemotherapy. CONCLUSION: Targeted therapies represent a paradigm shift in the treatment of FL. Further studies are needed to directly compare these targeted therapies and their combinations, as well as to investigate biomarkers predictive of response.
背景:滤泡性淋巴瘤(FL)的治疗以前主要集中在化疗免疫疗法上,由于患者耐受性、累积毒性和疾病难治性,这种疗法可能存在不利之处。靶向疗法可以产生深度缓解,并改善无进展生存期和总生存期,且不良事件谱更易于耐受。 方法:我们总结了当前关于滤泡性淋巴瘤一线和复发难治情况下靶向疗法的文献及关键临床试验。 结果:在FL中研究的靶向疗法包括免疫调节剂、抗CD20抗体、布鲁顿酪氨酸激酶(BTK)抑制剂、zeste同源物2(EZH2)抑制剂、磷酸肌醇3激酶(PI3K)抑制剂和B细胞淋巴瘤2(BCL-2)抑制剂。嵌合抗原受体(CAR-T)疗法和双特异性T细胞衔接器(BiTE)疗法在单药治疗以及与靶向疗法联合使用时也显示出前景。这些疗法即使在高危患者或先前对化疗或利妥昔单抗难治的患者中也表现出高总体缓解率、显著的无进展生存期和总生存期。不良事件差异很大,但通常可控,与化疗的累积毒性相比更具优势。 结论:靶向疗法代表了FL治疗的范式转变。需要进一步研究以直接比较这些靶向疗法及其联合方案,并研究预测反应的生物标志物。
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