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:Prognostic value of early bone marrow MRD status in CAR-T therapy for myeloma.
Prognostic value of early bone marrow MRD status in CAR-T therapy for myeloma.
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骨髓微小残留病(MRD)评估可预测多发性骨髓瘤(MM)患者生存,但CAR-T 后1个月骨髓仍常低细胞性,此时MRD阴性的价值尚不明确。
本研究分析2016年8月至2021年6月在梅奥诊所接受CAR-T 的MM患者1个月骨髓MRD状态。60例中78%在1个月时骨髓MRD阴性;其中85%(40/47)患者受累及未受累游离轻链(FLC)均降至正常以下。达到完全缓解或严格完全缓解者,1个月骨髓MRD阴性和FLC低于正常的比例更高。持续骨髓MRD阴性率为40%(19/47),由MRD阳性转阴率为5%(1/20)。1个月MRD阴性者中38%骨髓低细胞性;14例中7例恢复正常细胞性,中位恢复时间12个月(范围3个月至未达到)。与MRD阳性者相比,MRD阴性者PFS更长,且不受骨髓细胞性影响:中位2.9个月比17.5个月(p<0.0001)。1个月骨髓MRD阴性及FLC低于正常均与生存延长相关,支持继续评估CAR-T 后早期骨髓检查的预后价值。
Bone marrow (BM) assessment of minimal residual disease (MRD) is prognostic for survival in multiple myeloma (MM). BM is still hypocellular at month 1 post CAR-T, thus the value of MRD negative (MRDneg) status at this timepoint is unclear.
We examined the impact of month 1 BM MRD status in MM patients who received CART at Mayo Clinic between 8/2016 and 6/2021. Among 60 patients, 78% were BM-MRDneg at month 1; and 85% (40/47) of these patients also had decreased to less than normal level of both involved and uninvolved free light chain (FLC < NL). Patients who achieved CR/sCR had higher rates of month 1 BM-MRDneg and FLC < NL. The rate of sustained BM-MRDneg was 40% (19/47). Rate of conversion from MRDpos to MRDneg was 5%(1/20).
At month 1, 38%(18/47) of the BM-MRDneg were hypocellular. Recovery to normal cellularity was observed in 50%(7/14) with a median time to normalization at 12 months (range: 3-Not reached). Compared to Month 1 BM-MRDpos patients, patients who were BM-MRDneg had longer PFS irrespective of BM cellularity [PFS: 2. 9 months (95% CI, 1. 2-NR) vs. 17. 5 months (95% CI, 10. 4-NR), p < 0. 0001]. Month 1 BM-MRDneg and FLC below normal were associated with prolonged survival.
Our data support the continued evaluation of BM early post-CART infusion as a prognostic tool.
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