The differential effects of tumor burdens on predicting the net benefits of ssCART-19 cell treatment on r/r B-ALL patients.
The differential effects of tumor burdens on predicting the net benefits of ssCART-19 cell treatment on r/r B-ALL patients.
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DOI：
10.1038/s41598-021-04296-3
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发表时间：
2022-01-10
影响因子：
4.6
通讯作者：
Yu L
中科院分区：
文献类型：
--
作者：
Li M;Xue SL;Tang X;Xu J;Chen S;Han Y;Qiu H;Miao M;Xu N;Tan J;Kang L;Yu Z;Lou X;Xu Y;Chen J;Yan Z;Feng W;Wu D;Yu L
肿瘤负荷（TB）与CAR-T细胞引起的细胞因子释放综合征（CRS）的严重程度显著相关，但其与治疗效果的相关性尚未得到系统研究。本研究的重点是TB水平对ssCART-19治疗r/r B-ALL的安全性和有效性的影响。以5%肿瘤负荷为界，将研究对象分为高、低肿瘤负荷组。在这种分组策略下，我们分析了差异r/r B-ALL结核对ssCART-19细胞治疗后临床疗效（CR率和长期生存）和安全性的影响。本研究共报道78例患者。差异B-ALL结核显著影响ssCART-19治疗患者的完全缓解（CR）率，低TB组和高TB组的完全缓解率分别为93.94%和75.56% （P = 0.0358）。根据无事件生存期（EFS）和总生存期（OS）进一步研究结核对长期治疗疗效的影响；低TB组的OS和EFS均优于高TB组，但差异无统计学意义。重要的是，无论是在氟达拉滨-环磷酰胺（FC）前置化疗之前还是之后测量TB， TB测量的时间点都没有显著影响OS和EFS谱。另一方面，CRS严重程度与TB水平显著相关（P = 0.0080）， sCRS发病率与TB水平显著相关（sCRS发病率随TB水平升高而升高，P = 0.0224）。出乎意料的是，ssCART-19细胞扩增峰在研究组之间没有显著差异（P = 0.2951）。在安全性和CR率方面，低r/r B-ALL结核病患者比高TB患者从CAR-T治疗中获得更多的净收益。这些发现对于确定r/r B-ALL患者的最佳CAR-T细胞治疗窗口至关重要，并将进一步为r/r B-ALL患者的差异tb制定全面合理的CAR-T细胞治疗计划。试验注册：ClinicalTrials.gov识别码，NCT03919240。
The tumor burden (TB) is significantly related to the severity of cytokine release syndrome (CRS) caused by CAR-T cells, but its correlation with therapeutic efficacy has not been systematically studied. This study focused on the effects of the TB level on both the safety and efficacy of ssCART-19 as a treatment for r/r B-ALL. Taking the 5% tumor burden as the boundary, the study participants were divided into 2 groups, high and low tumor burden groups. Under this grouping strategy, the impacts of differential r/r B-ALL TBs on the clinical therapeutic efficacy (CR rate and long-term survival) and safety profiles after ssCART-19 cell treatment were analysed. 78 patients were reported in this study. The differential B-ALL TBs significantly affected the complete remission (CR) rates of patients treated with ssCART-19, with rates of 93.94% and 75.56% in the low and high TB groups, respectively (P = 0.0358). The effects of TBs on long-term therapeutic efficacy were further studied based on event-free survival (EFS) and overall survival (OS) profiles; both the OS and EFS of the low TB group were better than those of the high TB group, but the differences were not statistically significant. Importantly, the time points of TB measurement did not significantly affect the OS and EFS profiles regardless of whether the TBs were measured before or after fludarabine-cyclophosphamide (FC) preconditional chemotherapy. On the other hand, the severity of CRS was significantly correlated with the TB level (P = 0.0080), and the incidence of sCRS was significantly related to the TB level (the sCRS incidence increased as the TB level increased, P = 0.0224). Unexpectedly, the ssCART-19 cell expansion peaks were not significantly different (P = 0.2951) between the study groups. Patients with a low r/r B-ALL TB yield more net benefits from CAR-T treatment than those with a high TB in terms of safety and CR rate. These findings are critical and valuable for determining the optimal CAR-T cell treatment window for r/r B-ALL patients and will further the development of comprehensive and reasonable CAR-T cell treatment plans for r/r B-ALL patients with differential TBs. Trial registration: ClinicalTrials.gov identifier, NCT03919240.
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影响因子：
82.9
作者：
Giavridis T;van der Stegen SJC;Eyquem J;Hamieh M;Piersigilli A;Sadelain M
通讯作者：
Sadelain M
DOI：
10.1056/nejmoa1707447
发表时间：
2017-12-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Neelapu SS;Locke FL;Bartlett NL;Lekakis LJ;Miklos DB;Jacobson CA;Braunschweig I;Oluwole OO;Siddiqi T;Lin Y;Timmerman JM;Stiff PJ;Friedberg JW;Flinn IW;Goy A;Hill BT;Smith MR;Deol A;Farooq U;McSweeney P;Munoz J;Avivi I;Castro JE;Westin JR;Chavez JC;Ghobadi A;Komanduri KV;Levy R;Jacobsen ED;Witzig TE;Reagan P;Bot A;Rossi J;Navale L;Jiang Y;Aycock J;Elias M;Chang D;Wiezorek J;Go WY
通讯作者：
Go WY
影响因子：
11.4
作者：
Pan, J.;Yang, J. F.;Tong, C. R.
通讯作者：
Tong, C. R.
影响因子：
17.1
作者：
Brentjens RJ;Davila ML;Riviere I;Park J;Wang X;Cowell LG;Bartido S;Stefanski J;Taylor C;Olszewska M;Borquez-Ojeda O;Qu J;Wasielewska T;He Q;Bernal Y;Rijo IV;Hedvat C;Kobos R;Curran K;Steinherz P;Jurcic J;Rosenblat T;Maslak P;Frattini M;Sadelain M
通讯作者：
Sadelain M
影响因子：
3.9
作者：
Qu, Changju;Ping, Nana;Jin, Zhengming
通讯作者：
Jin, Zhengming