Chimeric Antigen Receptor-modified Donor Lymphocyte Infusion Improves the Survival of Acute Lymphoblastic Leukemia Patients With Relapsed Diseases After Allogeneic Hematopoietic Stem Cell Transplantation

Wang, Tao; Gao, Lei; Hu, Xiaoxia; Liu, Bin; Chen, Jie; Zhang, Weiping; Wang, Jianmin; Yu, Xiaolong; Feng, Dongge; Chang, Alfred E.; Wicha, Max; Tang, Gusheng; Li, Qiao; Yang, Jianmin

doi:10.1097/cji.0000000000000257

Cited by 12 publications

(16 citation statements)

References 36 publications

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“…used CAR T cells as DLI treatment, which significantly prolonged the survival period. They found a lower incidence of aGVHD than that of traditional DLI ( 31 ).…”

Section: Discussionmentioning

confidence: 91%

Efficacy and Safety of Chimeric Antigen Receptor T Cells in Acute Lymphoblastic Leukemia With Post-Transplant Relapse

et al. 2021

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Twenty patients with relapsed B-ALL after HSCT were treated with CAR T cell therapy and were evaluated for efficacy and safety. Twelve patients previously received haploidentical transplantation, while 8 patients received HLA-matched transplantation. The median relapse time was 12 months (range, 4 to 72). Thirteen patients received autologous CAR T cells, and 7 patients received allogeneic CAR T cells, which were derived from transplant donors. The median infusion dose was 2.9×106/kg (range, 0.33 to 12×106/kg). Nineteen patients were evaluated for efficacy, among which 17 patients (89.5%) achieved MRD negative. The CR rates in the HLA-matched transplantation group and haploidentical transplantation group were 100% (7/7) and 83.3% (10/12), respectively. The median follow-up time was 9.80 months (range, 2.40 to 64.97). Ten patients (50%) died of relapse, 3 patients (15%) died of infection, and 1 patient (5%) died of aGVHD. Fifteen patients (75%) developed CRS, including 3 (20%) grade 1 CRS, 6 (40%) grade 2 CRS, and 6 (40%) grade 3 CRS. Ten patients (50%) developed aGVHD, including 1 (10%) grade I aGVHD, 6 (60%) grade II aGVHD, and 3 (30%) grade III aGVHD. The log rank test showed that CAR T cell origin was correlated with aGVHD occurrence in the haploidentical transplantation group (P = 0.005). The authors’ study indicated that the initial efficacy and safety of CAR T cell therapy for patients with post-transplant relapse were satisfactory. However, aGVHD was a concern in patients with a history of haploidentical transplantation occupied with allogeneic CAR T cells, which warrants clinical attention.

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“…used CAR T cells as DLI treatment, which significantly prolonged the survival period. They found a lower incidence of aGVHD than that of traditional DLI ( 31 ).…”

Section: Discussionmentioning

confidence: 91%

Efficacy and Safety of Chimeric Antigen Receptor T Cells in Acute Lymphoblastic Leukemia With Post-Transplant Relapse

et al. 2021

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“…The two quasi-experimental studies assessing OS 31 , 32 showed longer OS with CAR-T versus DLI therapy in R/R B-ALL patients (Wang et al. 31 DLI median 3.7 months (range 0–65); CAR-T median 12 months (range 3–29); p = 0.049.…”

Section: Resultsmentioning

confidence: 99%

“…One RCT was reclassified as NRSI and another one was classified as an ongoing RCT and was not still included because of its preliminary status only providing immature data for its primary outcome. 28 Therefore, two RCTs 29 , 30 and nine NRSI (two quasi-experimental studies 31 , 32 and seven cohort studies) 33 – 39 assessing the use of CAR-T in 1221 participants with B-cell lymphoma or T or B-cell acute lymphoblastic leukemia were included in the review. A detailed list with reasons for exclusion is presented in Supplemental Appendix 2 .…”

Section: Resultsmentioning

confidence: 99%

Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies: a living systematic review on comparative studies

Saiz

Leache

Gutiérrez-Valencia

et al. 2023

Therapeutic Advances in Hematology

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Background: Chimeric antigen receptor T-cell (CAR-T) cell therapies have been claimed to be curative in responsive patients. Nonetheless, response rates can vary according to different characteristics, and these therapies are associated with important adverse events such as cytokine release syndrome, neurologic adverse events, and B-cell aplasia. Objectives: This living systematic review aims to provide a timely, rigorous, and continuously updated synthesis of the evidence available on the role of CAR-T therapy for the treatment of patients with hematologic malignancies. Design: A systematic review with meta-analysis of randomized controlled trials (RCTs) and comparative non-randomized studies of interventions (NRSI), evaluating the effect of CAR-T therapy versus other active treatments, hematopoietic stem cell transplantation, standard of care (SoC) or any other intervention, was performed in patients with hematologic malignancies. The primary outcome is overall survival (OS). Certainty of the evidence was determined using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Data sources and Methods: Searches were performed in the Epistemonikos database, which collates information from multiple sources to identify systematic reviews and their included primary studies, including Cochrane Database of Systematic Reviews, MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, DARE, HTA Database, Campbell database, JBI Database of Systematic Reviews and Implementation Reports, EPPI-Centre Evidence Library. A manual search was also carried out. We included the evidence published up to 1 July 2022. Results: We included the evidence published up to 1 July 2022. We considered 139 RCTs and 1725 NRSI as potentially eligible. Two RCTs ( N = 681) comparing CAR-T therapy with SoC in patients with recurrent/relapsed (R/R) B-cell lymphoma were included. RCTs did not show statistical differences in OS, serious adverse events, or total adverse events with grade ⩾ 3. Higher complete response with substantial heterogeneity [risk ratio = 1.59; 95% confidence interval (CI) = (1.30–1.93); I2 = 89%; 2 studies; 681 participants; very low certainty evidence] and higher progression-free survival [hazard ratio for progression or death = 0.49; 95% CI = (0.37–0.65); 1 study; 359 participants; moderate certainty evidence] were reported with CAR-T therapies. Nine NRSI ( N = 540) in patients with T or B-cell acute lymphoblastic leukemia or R/R B-cell lymphoma were also included, providing secondary data. In general, the GRADE certainty of the evidence for main outcomes was mostly low or very low. Conclusion: So far, assuming important limitations in the level of certainty due to scarce and heterogenous comparative studies, CAR-T therapies have shown some benefit in terms of progression-free survival, but no overall survival, in patients with R/R B-cell lymphoma. Despite one-arm trials have already facilitated approval of CAR-T cell treatments, additional evidence from large comparative studies is still needed to better characterize the benefit-harm ratio of the use of CAR-T in a variety of patient populations with hematological malignancies. Registration: https://doi.org/10.12688/openreseurope.14390.1 PROSPERO/OSF Preregistration: 10.17605/OSF.IO/V6HDX

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“…The details have been described previously. 19,20 Disease assessments were performed prior to and after ASCT therapy (1, 3, 6, 9, 12 months) with positron-emission tomography and computed tomography (PET/CT) or CT. Patient response was evaluated utilising the 2007 revised response criteria for malignant lymphoma.…”

Section: Study Design and Participantsmentioning

confidence: 99%

Chimeric antigen receptor T‐cell therapy combined with autologous stem cell transplantation improved progression‐free survival of relapsed or refractory diffuse large B‐cell lymphoma patients: A single‐center, retrospective, cohort study

Wang

Gao

et al. 2022

Hematological Oncology

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Autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell therapy (CART) are salvage therapies that are utilised for treatment of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).However, whether the combination therapy of ASCT and CART (ASCT-CART) can improve the survival of R/R DLBCL remains unknown. Overall, 67 R/R DLBCL patients were included, among which 21 patients underwent ASCT-CART therapy and 46 patients underwent ASCT therapy. The median number of mononuclear cells numbers that were infused in the ASCT-CART and ASCT groups was 4.71 � 10 8 /kg and 5.36 � 10 8 /kg, respectively (p = 0.469). The median number of CD34 + cell numbers that were infused in the ASCT-CART and ASCT groups was 2.41 � 10 6 /kg and 3.05 � 10 6 /kg, respectively (p = 0.663). The median number of CART cells that were infused was 2.63 � 10 6 /kg with a median transduction rate of 59.83%. The objective response rates to ASCT-CART and ASCT therapy were 90% and 89%, respectively (p = 1.000). However, the ASCT-CART group showed higher complete remission (CR) rates than the ASCT group (71% vs. 33%; p = 0.003). The ASCT-CART group demonstrated superior 3 year progression-free survival (PFS) (80% vs. 44%; p = 0.036) and lower 3 year relapse/progression rate (15% vs. 56%; p = 0.015) compared to the ASCT group. However, the 3 year overall survival results indicated that there were no differences between the two groups (80% vs. 69%; p = 0.545). For R/R DLBCL patients, ASCT-CART therapy is associated with higher CR rate, better PFS, and lower relapse/progression rate. These data support that ASCT-CART therapy can be used as a salvage therapy for R/R DLBCL patients.Tao Wang and Lili Xu are contributed equally to the manuscript.

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Chimeric Antigen Receptor-modified Donor Lymphocyte Infusion Improves the Survival of Acute Lymphoblastic Leukemia Patients With Relapsed Diseases After Allogeneic Hematopoietic Stem Cell Transplantation

Cited by 12 publications

References 36 publications

Efficacy and Safety of Chimeric Antigen Receptor T Cells in Acute Lymphoblastic Leukemia With Post-Transplant Relapse

Efficacy and Safety of Chimeric Antigen Receptor T Cells in Acute Lymphoblastic Leukemia With Post-Transplant Relapse

Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies: a living systematic review on comparative studies

Chimeric antigen receptor T‐cell therapy combined with autologous stem cell transplantation improved progression‐free survival of relapsed or refractory diffuse large B‐cell lymphoma patients: A single‐center, retrospective, cohort study

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