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:Time-Dependent Prognostic Value of Serological and Measurable Residual Disease Assessments after Idecabtagene Vicleucel.
Time-Dependent Prognostic Value of Serological and Measurable Residual Disease Assessments after Idecabtagene Vicleucel.
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在接受了嵌合抗原受体(CAR)T细胞治疗的多发性骨髓瘤患者中,可测量残留病(MRD)的作用尚不确定。我们分析了KarMMa研究中125例接受idecabtagene vicleucel(ide-cel)输注的复发/难治性多发性骨髓瘤患者在输注后第一年内的MRD动力学。在ide-cel治疗后1个月,未达完全缓解(CR)的患者与达到CR的患者在无进展生存期(PFS)方面没有差异;在这一时间节点,只有MRD状态可预测PFS存在显著差异。在3个月及以后MRD不可检测的患者中,达到CR者的PFS长于<CR者。持续存在于10-6对数范围的MRD以及MRD阴性患者中正常浆细胞的重新出现与较差的PFS相关。本研究揭示了ide-cel治疗后血清学和MRD反应动力学具有不同的预后意义,并提示研究正常浆细胞重新出现作为CAR-T 细胞功能丧失替代指标的潜在价值。意义:这是首批评估复发/难治性多发性骨髓瘤患者CAR-T 治疗后CR和MRD动力学影响的研究之一。这些数据有助于解读CAR-T 细胞输注后早期和晚期时间点血清学和MRD反应的预后意义。参见Landgren和Kazandjian的相关评论,第346页。本文收录于本期精选文章,第337页。
UNLABELLED: The role of measurable residual disease (MRD) in multiple myeloma patients treated with chimeric antigen receptor (CAR) T cells is uncertain.
We analyzed MRD kinetics during the first year after idecabtagene vicleucel (ide-cel) infusion in 125 relapsed/refractory multiple myeloma patients enrolled in KarMMa. At month 1 after ide-cel, there were no differences in progression-free survival (PFS) between patients in less than complete response (CR) versus those in CR; only MRD status was predictive of significantly different PFS at this landmark.
In patients with undetectable MRD at 3 months and beyond, PFS was longer in those achieving CR versus <CR. Persistent MRD in the 10-6 logarithmic range and reappearance of normal plasma cells in MRD-negative patients were associated with inferior PFS.
This study unveils different prognostic implications of serological and MRD response dynamics after ide-cel and suggests the potential value of studying the reappearance of normal plasma cells as a surrogate of loss of CAR T-cell functionality. SIGNIFICANCE: This is one of the first studies evaluating the impact of CR and MRD dynamics after CAR T therapy in relapsed/refractory multiple myeloma.
These data help interpret the prognostic significance of serological and MRD responses at early and late time points after CAR T-cell infusion. See related commentary by Landgren and Kazandjian, p. 346 . This article is featured in Selected Articles from This Issue, p. 337.
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