1.
Comparison of blinatumomab and CAR T-cell therapy in relapsed/refractory acute lymphoblastic leukemia: a systematic review and meta-analysis
Zhai, Y., Hong, J., Wang, J., Jiang, Y., Wu, W., Lv, Y., Guo, J., Tian, L., Sun, H., Li, Y., et al
Expert review of hematology. 2023
Abstract
OBJECTIVES This study evaluated the benefits and risks of patients with refractory or relapsed acute lymphocytic leukemia (R/R ALL) treated with Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy and blinatumomab. METHODS PubMed, Web of Science, Embase, and the Cochrane Library were searched for relevant studies. RESULTS The pooled complete remission (CR) rate and minimal residual disease (MRD) negative rate were 48%, 31% for blinatumomab, and 86% and 80% for CAR T-cell therapy. CONCLUSIONS The CAR T-cell therapy group exhibited a higher likelihood of CR rate than the blinatumomab group in every analysis regardless of adjustment subgroups. CAR T-cell therapy was associated with a significantly prolonged overall survival (OS) and relapse-free survival (RFS) compared with blinatumomab (2-year OS 55% vs 25%; 2-year RFS 40% vs 22%). CAR T-cell therapy was more effective for achieving CR and bridging to allogeneic hematopoietic stem cell transplantation (allo-SCT) than blinatumomab (2-year OS 75% vs. 57%). An emerging role for blinatumomab is as a bridging agent pre-SCT and for patients who achieve an MRD-negative state pre-SCT, post-SCT outcomes are expected to be the same as CAR-T. For adverse effects (AEs), blinatumomab was associated with a lower rate of grade ≥ 3 hematological toxicity, CRS, and neurological events.
2.
Anti-CD19 CAR-T cell therapy bridge to HSCT decreases the relapse rate and improves the long-term survival of R/R B-ALL patients: a systematic review and meta-analysis
Hu, L., Charwudzi, A., Li, Q., Zhu, W., Tao, Q., Xiong, S., Zhai, Z.
Annals of hematology. 2021
Abstract
Chimeric antigen receptor (CAR) T cell therapy improves the remission rate of refractory/relapsed B-acute lymphoblastic leukemia (R/R B-ALL) patients, but the relapse rate remains high. Recent studies suggest patients who underwent post-chimeric antigen receptor T cell therapy hematopoietic stem cell transplantation (post- HSCT) would achieve durable remission and better survival, but this remains controversial. To this end, we conducted a meta-analysis to assess the role of post-HSCT in R/R B-ALL. The Cochrane Library, Embase, and PubMed were used to identify relevant studies; the latest search update was on July 05, 2020. We used the Cochran Q test and I-squared statistics to test for heterogeneity among the studies analyzed. The fixed model and random model were used to combine results when appropriate. We performed all statistical analyses with Stata 12, and P < 0.05 was considered statistically significant. We included 18 studies with 758 patients in the meta-analysis. Our results indicated that post-HSCT was associated with lower relapse rate (RR: 0.40, 95% CI: 0.32-0.50, P = 0.000), better overall survival (HR: 0.37, 95% CI: 0.19-0.71, P = 0.003), better leukemia-free survival (HR: 0.20, 95% CI: 0.10-0.40, P = 0.000). However, post-HSCT did not influence OS in Caucasians, and CAR-T cells with CD28 co-stimulation factor bridged to HSCT did not influence OS. Post-HSCT decreased the relapse rate and improved the long-term survival of R/R B-ALL patients. R/R B-ALL patients would benefit from post-HSCT after CAR-T cell therapy.
3.
Consolidative Hematopoietic Stem Cell Transplantation After CD19 CAR-T Cell Therapy for Acute Lymphoblastic Leukemia: A Systematic Review and Meta-analysis
Xu, X., Chen, S., Zhao, Z., Xiao, X., Huang, S., Huo, Z., Li, Y., Tu, S.
Frontiers in oncology. 2021;11:651944
Abstract
BACKGROUND This study aimed to systematically evaluate and compare the efficacy and safety of consolidative hematopoietic stem cell transplantation (HSCT) after CD19 chimeric antigen receptor T (CAR-T) therapy with non-HSCT in the treatment of acute lymphoblastic leukemia (ALL). METHODS The PubMed, Embase, Cochrane Library and Web of Science databases were searched for clinical trials. Pooled hazard ratios (HRs) for overall survival (OS), relapse rate, and leukemia-free survival (LFS) as well as overall incidence rates for transplant-related mortality (TRM), acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), and infections were calculated using Stata software. RESULTS We screened 3,441 studies and identified 19 eligible studies with 690 patients. Among the patients who achieved complete remission (CR) after CD19 CAR-T therapy, consolidative HSCT was beneficial for OS (HR = 0.34, 95% CI, 0.170.68, P = 0.003), the relapse rate (HR = 0.16, 95% CI, 0.100.25, P < 0.001), and LFS (HR = 0.15, 95% CI, 0.080.28, P < 0.001). For patients who achieved MRD-negative (neg) CR after CD19 CAR-T therapy, consolidative HSCT was beneficial for OS (0.57, 95% CI, 0.330.99, P = 0.045), the relapse rate (0.14, 95% CI, 0.060.31, P < 0.001), and LFS (0.21, 95% CI, 0.120.35, P < 0.001). Regarding safety, we calculated pooled incidence rates for TRM (8%, 95% CI, 0.020.15), aGVHD (44%, 95% CI, 0.230.67), cGVHD (36%, 95% CI, 0.170.56), and infections (39%, 95% CI, 0.030.83). CONCLUSIONS Compared with non-HSCT treatment, consolidative HSCT after CD19 CAR-T therapy for R/R B-ALL patients can prolong OS and LFS and reduce the risk of relapse. The incidence rates for adverse events are acceptable. More high-quality randomized controlled trials are required to avoid bias and further determine the efficacy of HSCT.