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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Nutritional status indices on the prognosis of patients with relapsed and refractory multiple myeloma treated with CAR-T cell immunotherapy.
Nutritional status indices on the prognosis of patients with relapsed and refractory multiple myeloma treated with CAR-T cell immunotherapy.
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本研究确立治疗前 CONUT 和 PNI 是接受 CAR-T 治疗的 R/R MM 患者的重要预后预测因素。
嵌合抗原受体(CAR)T细胞疗法治疗复发/难治性多发性骨髓瘤(R/R MM)疗效显著。由控制营养状态(CONUT)和预后营养指数(PNI)等客观指标评估的营养状况,会影响MM预后,但这些指标对R/R MM患者接受CAR-T 治疗后结局的预测价值仍不清楚。
研究者回顾性分析了181例接受CAR-T 治疗的R/R MM患者。根据ROC分析确定的CONUT最佳截断值6.5和PNI截断值42.75对患者进行分层,并考察CONUT/PNI与治疗结局的关系。
与高CONUT或低PNI患者相比,低CONUT或高PNI患者的无进展生存期(PFS)和总生存期(OS)显著更长。总体客观缓解率(ORR)较高,约为90%–95%,但CONUT或PNI不同亚组间无显著差异。重要的是,低CONUT或高PNI与造血恢复更快(红细胞、血红蛋白、血小板、中性粒细胞、CD4+及CD8+ T细胞)、长期血液学毒性(PHT)发生率较低,以及CAR转基因峰值水平较高相关。不同亚组的细胞因子释放综合征(CRS)或免疫效应细胞相关神经毒性综合征(ICANS)严重程度无显著差异。多因素分析证实,高CONUT是PFS和OS较差的独立危险因素,而低PNI是PFS较差的独立危险因素。
本研究证实,治疗前CONUT和PNI是接受CAR-T 治疗的R/R MM患者的重要预后预测指标。低CONUT或高PNI患者长期生存结局更佳,这可能与造血恢复和CAR-T 细胞扩增增强有关。研究结果凸显了营养评估在预后判断中的重要性,并可能为未来优化CAR-T 治疗结局的策略提供指导。
We conducted a retrospective analysis of 181 R/R MM patients receiving CAR-T therapy. Patients were stratified by optimal CONUT (cutoff: 6.5) and PNI (cutoff: 42.75) scores determined via ROC analysis. Associations between CONUT/PNI and treatment outcomes were investigated.
Patients with low CONUT or high PNI exhibited significantly improved progression-free survival (PFS) and overall survival (OS) compared to their counterparts (high CONUT or low PNI). While objective response rates (ORR) were high overall (approximately 90-95%), they did not differ significantly between CONUT or PNI subgroups. Importantly, low CONUT or high PNI was associated with faster hematopoietic recovery (red blood cells, hemoglobin, platelets, neutrophils, CD4+, CD8 + T-cells), lower incidence of prolonged hematologic toxicity (PHT), and higher peak CAR transgene levels. No significant differences were observed in cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) severity between subgroups. Multivariate analysis confirmed high CONUT as an independent risk factor for inferior PFS and OS, while low PNI was an independent risk factor for inferior PFS.
This study establishes pretreatment CONUT and PNI as significant prognostic predictors for R/R MM patients undergoing CAR-T therapy. Patients with low CONUT or high PNI experience superior long-term survival outcomes, potentially linked to enhanced hematopoietic recovery and CAR-T cell expansion. These findings underscore the importance of nutritional assessment in prognostication and may guide future strategies to optimize CAR-T outcomes in R/R MM.
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