不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel:ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:A new era for transplant-ineligible R/R LBCL patients: what's changing?
A new era for transplant-ineligible R/R LBCL patients: what's changing?
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大多数大B细胞淋巴瘤(LBCL)患者通过一线化学免疫治疗可获治愈;然而,30-40%的患者会出现复发/难治性(R/R)疾病。历史上,挽救性化疗后行自体干细胞移植(ASCT)是标准的二线治疗方案。多项研究表明,原发难治或早期复发的LBCL患者从ASCT中获益有限。随着嵌合抗原受体(CAR)T细胞疗法的出现,R/R LBCL的预后已发生显著改变。TRANSFORM和ZUMA-7试验显示其疗效优越且毒性可控,促使lisocabtagene maraleucel(liso-cel)和axicabtagene ciloleucel(axi-cel)获批作为二线治疗选择。
重要的是,这些试验要求参与者医学上适合接受ASCT。本综述聚焦于不适合移植的R/R LBCL患者的治疗选择。II期PILOT研究表明,liso-cel在医学上不适合的患者中有效,支持将ASCT不合格患者定义为独立类别。其他活跃的治疗选择包括抗体药物偶联物、双特异性抗体联合化疗,以及其他新型免疫疗法,这些在该难治人群中显示出有前景的缓解率。
Most patients with large B-cell lymphoma (LBCL) are cured with frontline chemoimmunotherapy; however, 30-40% experience relapsed or refractory (R/R) disease. Historically, salvage chemotherapy followed by autologous stem cell transplantation (ASCT) represented the standard second-line treatment. Several studies have demonstrated that patients with primary refractory or early-relapsed LBCL derive limited benefit from ASCT.
With the advent of chimeric antigen receptor (CAR) T-cell therapy, the prognosis of R/R LBCL has changed substantially. The TRANSFORM and ZUMA-7 trials, which showed superior efficacy and manageable toxicity, led to the approval of lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) as second-line options.
Importantly, these trials required participants to be medically fit for ASCT. This review focuses on therapeutic options for transplant-ineligible patients with R/R LBCL. The phase II PILOT study demonstrated that liso-cel is effective in medically unfit individuals, supporting the definition of a distinct category of ASCT-ineligible patients.
Additional active options include antibody-drug conjugates, bispecific antibodies in combination with chemotherapy, and other novel immunotherapies, which have shown promising response rates in this difficult-to-treat population.
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