CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Prospects in the management of patients with follicular lymphoma beyond first-line therapy.
Prospects in the management of patients with follicular lymphoma beyond first-line therapy.
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过去十年中,复发/难治性滤泡性淋巴瘤患者的管理发生了显著变化,新一类药物(磷脂酰肌醇3-激酶抑制剂、免疫调节剂、表观遗传疗法和CAR-T 细胞)的出现补充了已有的多种方法(细胞毒性药物、抗CD20抗体、放疗、放射免疫治疗以及自体与异基因移植)。临床情景的多样性、来自II期研究的大量数据以及缺乏比较治疗策略的随机研究,使得无法给出明确的推荐意见,需要个体化决策。早期进展的患者需要特别关注,因为存在组织学转化的风险且对标准治疗反应较低。在治疗排序时,必须考虑既往治疗方案以及未来治疗线的潜在需求。应仔细评估现有选项的风险与预期获益——这些因地区和社经因素而异——并应纳入患者的目标。鉴于这些患者可能存活数年至数十年且可能接受多线治疗,维持其生活质量至关重要。当前格局很可能继续快速演变,其他有效药物不断涌现(尤其是双特异性抗体和其他靶向治疗),多种联合方案正在评估中。希望正在开发的新治疗能够实现更长的无进展间期并尽量减少毒性。对疾病生物学及这些不同药物机制的更深入理解,应能为在疾病各阶段选择最优治疗提供进一步见解。
The management of patients with relapsed or refractory follicular lymphoma has evolved markedly in the last decade, with the availability of new classes of agents (phosphoinositide 3-kinase inhibitors, immunomodulators, epigenetic therapies, and chimeric antigen receptor T cells) supplementing the multiple approaches already available (cytotoxic agents, anti-CD20 antibodies, radiation therapy, radioimmunotherapy, and autologous and allogeneic transplants). The diversity of clinical scenarios, the flood of data derived from phase II studies, and the lack of randomized studies comparing treatment strategies preclude firm recommendations and require personalized decisions. Patients with early progression require specific attention given the risk of histological transformation and their lower response to standard therapies. In sequencing therapies, one must consider prior treatment regimens and the potential need for future lines of therapy.
Careful evaluation of risks and expected benefits of available options, which vary depending on location and socioeconomics, should be undertaken, and should incorporate the patient's goals. Preserving quality of life for these patients is essential, given the likelihood of years to decades of survival and the possibility of multiple lines of therapy.
The current landscape is likely to continue evolving rapidly with other effective agents emerging (notably bispecific antibodies and other targeted therapies), and multiple combinations being evaluated. It is hoped that new treatments under development will achieve longer progression-free intervals and minimize toxicity. A better understanding of disease biology and the mechanisms of these different agents should provide further insights to select the optimal therapy at each stage of disease.
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