1.
Cytoplasmic CD79a is a promising biomarker for B lymphoblastic leukemia follow up post CD19 CAR-T therapy
Chen, M., Fu, M., Wang, A., Wu, X., Zhen, J., Gong, M., Zhang, X., Yue, G., Du, Q., Zhao, W., et al
Leukemia & lymphoma. 2022;63(2):426-434
Abstract
Minimal residual disease (MRD) detection is an important prognostic parameter in patients with refractory or relapsed B-cell acute lymphoblastic leukemia (R/R B-ALL). CD79a has been reported to exhibit a high degree of linage-specificity for B-cell differentiation, with a specificity of 88% and a sensitivity of 100%. In this study, we investigated the efficiency and prognostic role of cytoplasmic CD79a (cCD79a) antibody-gated multicolor flow cytometry (MFC) in MRD detection in patients with B-ALL who received CD19-targeted chimeric antigen receptor (CAR) T-cell therapy bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT). The retrospective analysis was carried on to 59 patients who accepted allo-HSCT after CD19-CAR-T infusion from June 2016 to May 2017. The MFC MRD statuses before and after allo-HSCT were both strongly correlated with the transplantation prognosis, the MFC panel with cCD79a gating can effectively monitor MRD after CD19 CAR T-cell therapy and predict the prognosis after allo-HSCT. Trial registration: ClinicalTrials#: ChiCTR-IIh-16008711.gov: NCT03173417. Registered 30 May 2017 - retrospectively registered, https://www.clinicaltrials.gov/.
2.
Efficacy and safety of anti-CD19 CAR T-cell therapy in 110 patients with B-cell acute lymphoblastic leukemia with high-risk features
Zhang, X., Lu, X. A., Yang, J., Zhang, G., Li, J., Song, L., Su, Y., Shi, Y., Zhang, M., He, J., et al
Blood advances. 2020;4(10):2325-2338
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Abstract
Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is effective in patients with advanced B-cell acute lymphoblastic leukemia (B-ALL). However, efficacy data is sparse in subgroups of patients with high-risk features such as BCR-ABL+, TP53 mutation, extramedullary disease (including central nervous system leukemia) or posttransplant relapse. It is also uncertain whether there is an added benefit of transplantation after anti-CD19 CAR T-cell therapy. We conducted a phase 1/2 study of 115 enrolled patients with CD19+ B-ALL. A total of 110 patients were successfully infused with anti-CD19 CAR T cells. In all, 93% of patients achieved a morphologic complete remission, and 87% became negative for minimal residual disease. Efficacy was seen across all subgroups. One-year leukemia-free survival (LFS) was 58%, and 1-year overall survival (OS) was 64% for the 110 patients. Seventy-five nonrandomly selected patients (73.5%) subsequently received an allogeneic hematopoietic stem cell transplant (allo-HSCT). LFS (76.9% vs 11.6%; P < .0001; 95% confidence interval [CI], 11.6-108.4) and OS (79.1% vs 32.0%; P < .0001; 95% CI, 0.02-0.22) were significantly better among patients who subsequently received allo-HSCT compared with those receiving CAR T-cell therapy alone. This was confirmed in multivariable analyses (hazard ratio, 16.546; 95% CI, 5.499-49.786). Another variate that correlated with worse outcomes was TP53 mutation (hazard ratio, 0.235; 95% CI, 0.089-0.619). There were no differences in complete remission rate, OS, or LFS between groups of patients age 2 to 14 years or age older than 14 years. Most patients had only mild cytokine release syndrome and neurotoxicity. Our data indicate that anti-CD19 CAR T-cell therapy is safe and effective in all B-ALL subgroups that have high-risk features. The benefit of a subsequent allo-HSCT requires confirmation because of nonrandom allocation. This trial was registered at www.clinicaltrials.gov as #NCT03173417.
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Anti-CD19 CAR-T Therapy Bridging to Allo-HSCT for Relapsed/refractory B-cell Acute Lymphoblastic Leukemia: An Open-Label Pragmatic Clinical Trial
Jiang, H., Li, C., Yin, P., Guo, T., Liu, L., Xia, L., Wu, Y., Zhou, F., Ai, L., Shi, W., et al
American journal of hematology. 2019
Abstract
Chimeric antigen receptor-modified T-cell (CAR-T) therapy is effective and safe for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), but its value has been limited in terms of long-term leukemia-free survival. New strategies that can help CAR-T therapy achieve lasting effect are urgently warranted. This non-randomized interventional pragmatic clinical trial aimed to explore whether consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT) could improve the long-term prognosis of the minimal residual disease-negative complete remission (MRD(-) CR) patients after CAR-T therapy. In the first stage, 58 r/r B-ALL patients received split doses of CAR-T cells after lymphodepleting chemotherapy, and 51 (87.9%) achieved CR. In the second stage, 21/47 MRD(-) CR patients without previous allo-HSCT and contraindications or other restrictions, on their own accord, received consolidative allo-HSCT within three months after CAR-T therapy. There was no difference in overall survival (OS) between the MRD(-) CR patients who received allo-HSCT and those who didn't, but event-free survival (EFS) and relapse-free survival (RFS) were significantly prolonged by allo-HSCT in the subgroups with either high (≥ 5%) pre-infusion bone marrow MRD assessed by flow cytometry (BM-FCM-MRD) or poor prognostic markers (P < 0.05). However, no difference was found in EFS and RFS for patients with pre-infusion BM-FCM-MRD < 5% and without poor prognostic markers (P > 0.05). To conclude, CAR-T therapy bridging to allo-HSCT is a safe and effective therapeutic strategy for r/r B-ALL patients, and may prolong their EFS and RFS, especially when they have high pre-infusion BM-FCM-MRD or poor prognostic markers. This article is protected by copyright. All rights reserved.