1.
CD19/CD22 dual-targeting chimeric antigen receptor T-cell therapy bridging to allogeneic haematopoietic stem cell transplantation for B-cell acute lymphoblastic leukaemia delays platelet recovery and increases risks of cytomegalovirus and Epstein-Barr virus viremia after transplantation
Li, S., Ge, J., Zhou, S., Zhu, W., Han, Y., Chen, S., Xue, S., Wang, Y., Qiu, H., Wu, X., et al
Clinical and translational medicine. 2023;13(10):e1459
2.
Identification of the Predictive Models for the Treatment Response of Refractory/Relapsed B-Cell ALL Patients Receiving CAR-T Therapy
Gu, J., Liu, S., Cui, W., Dai, H., Cui, Q., Yin, J., Li, Z., Kang, L., Qiu, H., Han, Y., et al
Frontiers in immunology. 2022;13:858590
Abstract
BACKGROUND/AIMS: Chimeric antigen receptor (CAR) T cells for refractory or relapsed (r/r) B-cell acute lymphoblastic leukemia (ALL) patients have shown promising clinical effectiveness. However, the factors impacting the clinical response of CAR-T therapy have not been fully elucidated. We here aimed to identify the independent factors of CAR-T treatment response and construct the models for predicting the complete remission (CR) and minimal residual disease (MRD)-negative CR in r/r B-ALL patients after CAR-T cell infusion. METHODS Univariate and multivariate logistic regression analyses were conducted to identify the independent factors of CR and MRD-negative CR. The predictive models for the probability of remission were constructed based on the identified independent factors. Discrimination and calibration of the established models were assessed by receiver operating characteristic (ROC) curves and calibration plots, respectively. The predictive models were further integrated and validated in the internal series. Moreover, the prognostic value of the integration risk model was also confirmed. RESULTS The predictive model for CR was formulated by the number of white blood cells (WBC), central neural system (CNS) leukemia, TP53 mutation, bone marrow blasts, and CAR-T cell generation while the model for MRD-negative CR was formulated by disease status, bone marrow blasts, and infusion strategy. The ROC curves and calibration plots of the two models displayed great discrimination and calibration ability. Patients and infusions were divided into different risk groups according to the integration model. High-risk groups showed significant lower CR and MRD-negative CR rates in both the training and validation sets (p < 0.01). Furthermore, low-risk patients exhibited improved overall survival (OS) (log-rank p < 0.01), higher 6-month event-free survival (EFS) rate (p < 0.01), and lower relapse rate after the allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T cell infusion (p = 0.06). CONCLUSIONS We have established predictive models for treatment response estimation of CAR-T therapy. Our models also provided new clinical insights for the accurate diagnosis and targeted treatment of r/r B-ALL.
3.
Comparation of CART19 and autologous stem-cell transplantation for refractory/relapsed non-Hodgkin's lymphoma
Li, C., Zhang, Y., Zhang, C., Chen, J., Lou, X., Chen, X., Kang, L., Xu, N., Li, M., Tan, J., et al
JCI insight. 2019;5
Abstract
BACKGROUND Autologous stem-cell transplantation (ASCT) is the standard treatment for R/R B-NHL, while chimeric antigen receptor T (CAR-T) therapy targeting CD19 emerges as an alternative strategy. Here we report a comparative analysis of the two strategies in a single center. METHODS We performed a prospective single-arm study of CAR-T therapy in 29 patients with R/R B-NHL and compared the outcomes with contemporaneous 27 patients who received ASCT. NHL was diagnosed by histopathological assessments, and the safety and efficacy were compared. RESULTS The CAR-T group exhibited better rates of CR (48.0% vs. 20.8%, P=0.046) and one-year OS (74.4% vs. 44.5%, P=0.044) compared with the ASCT group. Subpopulation analysis showed that patients with IPI scores ≥ 3 achieved significantly higher ORR and CR rates in the CAR-T group than in the ASCT group (ORR: 72.0% vs. 10.0%, P=0.002; CR: 38.9% vs 0% P=0.030, respectively). The most common severe adverse events in the CAR-T group were cytokine release syndrome, neurotoxicity and infection compared with cytopenia, gastrointestinal toxicity and infection in the ASCT group. Additionally, the incidence of non-hematologic severe adverse events (SAEs) was markedly lower in the CAR-T group than in the ASCT group (20.7% vs. 48.1% P=0.030). CONCLUSION CAR-T therapy exhibited superior clinical outcomes in safety and efficacy over ASCT in patients with R/R B-NHL, suggesting CAR-T may be a recommended alternative to ASCT.