scholarly journals Efficacy and Safety of CD28- or 4-1BB-Based CD19 CAR-T Cells in B Cell Acute Lymphoblastic Leukemia

2020 ◽  
Vol 18 ◽  
pp. 272-281 ◽  
Author(s):  
Xiangyu Zhao ◽  
Junfang Yang ◽  
Xian Zhang ◽  
Xin-An Lu ◽  
Min Xiong ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Efficacy And Safety ◽  
Car T Cells ◽  
Car T ◽  
Cell Acute Lymphoblastic Leukemia

The ABCs of Immunotherapy for Adult Patients With B-Cell Acute Lymphoblastic Leukemia

2017 ◽  
Vol 52 (3) ◽  
pp. 268-276 ◽  
Author(s):  
Troy Z. Horvat ◽  
Amanda N. Seddon ◽  
Adebayo Ogunniyi ◽  
Amber C. King ◽  
Larry W. Buie ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Data Extraction ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Efficacy And Safety ◽  
Car T Cells ◽  
Car T ◽  
American Society

Objective: To review the pharmacology, efficacy, and safety of Food and Drug Administration approved and promising immunotherapy agents used in the treatment of acute lymphoblastic leukemia (ALL). Data Sources: A literature search was performed of PubMed and MEDLINE databases (1950 to July 2017) and of abstracts from the American Society of Hematology and the American Society of Clinical Oncology. Searches were performed utilizing the following key terms: rituximab, blinatumomab, inotuzumab, ofatumumab, obinutuzumab, Blincyto, Rituxan, Gazyva, Arzerra, CAR T-cell, and chimeric antigen receptor (CAR). Study Selection/Data Extraction: Studies of pharmacology, clinical efficacy, and safety of rituximab, ofatumumab, obinutuzumab, inotuzumab, blinatumomab, and CAR T-cells in the treatment of adult patients with ALL were identified. Data Synthesis: Conventional chemotherapy has been the mainstay in the treatment of ALL, producing cure rates of approximately 90% in pediatrics, but it remains suboptimal in adult patients. As such, more effective consolidative modalities and novel therapies for relapsed/refractory disease are needed for adult patients with ALL. In recent years, anti-CD20 antibodies, blinatumomab, inotuzumab, and CD19-targeted CAR T-cells have drastically changed the treatment landscape of B-cell ALL. Conclusion: Outcomes of patients with relapsed disease are improving thanks to new therapies such as blinatumomab, inotuzumab, and CAR T-cells. Although the efficacy of these therapies is impressive, they are not without toxicity, both physical and financial. The optimal sequencing of these therapies still remains a question.

The Evolution and Future of CAR T Cells for B‐Cell Acute Lymphoblastic Leukemia

2017 ◽  
Vol 103 (4) ◽  
pp. 591-598 ◽  
Author(s):  
Colleen E. Annesley ◽  
Corinne Summers ◽  
Francesco Ceppi ◽  
Rebecca A. Gardner
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Car T Cells ◽  
Car T ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals Role of CAR-T cell therapy in B-cell acute lymphoblastic leukemia

2019 ◽  
Vol 13 (1) ◽  
pp. 36-42 ◽  
Author(s):  
Hildegard T. Greinix
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
Response Rate ◽  
Lymphoblastic Leukemia ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T ◽  
Cell Acute Lymphoblastic Leukemia

SummaryChimeric antigen receptor (CAR) T cells are genetically engineered cells containing fusion proteins combining an extracellular epitope-specific binding domain, a transmembrane and signaling domains of the T cell receptor. The CD19-CAR T cell product tisagenlecleucel has been approved by the US Food and Drug Administration and the European Medicines Agency for therapy of children and young adults under 25 years with relapsed/refractory B‑cell acute lymphoblastic leukemia (ALL) due to a high overall response rate of 81% at 3 months after therapy. The rates of event-free and overall survival were 50 and 76% at 12 months. Despite the high initial response rate with CD19-CAR‑T cells in B‑ALL, relapses occur in a significant fraction of patients. Current strategies to improve CAR‑T cell efficacy focus on improved persistence of CAR‑T cells in vivo, use of multispecific CARs to overcome immune escape and new CAR designs. The approved CAR‑T cell products are from autologous T cells generated on a custom-made basis with an inherent risk of production failure. For large scale clinical applications, universal CAR‑T cells serving as “off-the-shelf” agents would be of advantage. During recent years CAR‑T cells have been frequently used for bridging to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with relapsed/refractory B‑ALL since we currently are not able to distinguish those CAR‑T cell induced CRs that will persist without further therapy from those that are likely to be short-lived. CAR‑T cells are clearly of benefit for treatment following relapse after allogeneic HSCT. Future improvements in CAR‑T cell constructs may allow longer term remissions without additional HSCT.

scholarly journals Tandem CD19/CD22 Dual Targets CAR-T Cells Therapy Obtains Superior CR Rate Than Single CD19 CAR-T Cells Infusion As Well As Sequential CD19 and CD22 CAR-T Cells Infusion for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1755-1755
Author(s):  
Sining Liu ◽  
Xinyue Zhang ◽  
Haiping Dai ◽  
Qingya Cui ◽  
Wei Cui ◽  
...  
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Car T Cells ◽  
Significant Difference ◽  
Car T ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Background: CD19 chimeric antigen receptor T (CAR-T) cells therapy has shown great success in B-cell acute lymphoblastic leukemia (B-ALL). To reduce the possibility of relapse due to CD19 antigen loss, sequential CD19/CD22 and tandem CD19/CD22 dual targets CAR-T cells have been developed. However, the optimal combination strategy of target antigens for CAR-T cells is still uncertain. This study was designed to compare the efficacy and safety of single CD19, tandem CD19/CD22 and sequential CD19/CD22 CAR-T cells therapies in relapsed/refractory(R/R) B-ALL patients. Methods: Between March 2016 and August 2020, a total of 200 patients with R/R B-ALL successfully received 230 CAR-T treatments (30 patients received the second CAR-T therapy and 8 patients received the third CAR-T therapy) were screened in this study. Among them, 168 patients received single CD19 CAR-T therapy, 49 patients received tandem CD19/CD22 CAR-T therapy, and 13 patients received sequential CD19/CD22 CAR-T therapy. ALL patients enrolled in the CD19 CAR-T clinical trials (NCT03919240) or CD19/CD22 CAR-T clinical trials (NCT03614858). Results: The baseline characteristics of patients were similar among the three groups. The complete remission (CR) rates were 82.7% (139/168) in patients who received CD19 CAR-T therapy, 95.9% (47/49) in patients who received tandem CD19/CD22 CAR-T therapy, and 69.2% (9/13) in patients who received sequential CD19/CD22 CAR-T therapy (P=0.012). Tandem CD19/CD22 CAR-T therapy remained one of the significant favorable factors in multivariate logistic regression analysis of CR rate in all patients (hazard ratio, 0.081; 95% CI, 0.010-0.671). Furthermore, minimal residual disease (MRD)-negative CR rates were 66.7%, 81.6% and 61.5%, respectively (P=0.092). There was no significant difference in the incidence of adverse events among the three groups. Severe cytokine release syndrome (CRS, Grade ≥ 3) occurred in 25.0% of patients in CD19 group, 18.4% of patients in tandem CD19/CD22 group, and 23.1% in sequential CD19/CD22 group (P=0.641). There was no significant difference in overall survival (OS) and leukemia-free survival (LFS) among three groups (6-month OS: 83.1%, 90.0% and 88.9%, respectively, P=0.1620; 6-month LFS: 76.2%, 76.2% and 88.9%, respectively, P=0.8179). Univariate and multivariate Cox regression analyses showed that a better LFS related to less frequencies of relapse, lower tumor burden, MRD-negative CR and bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT). Conclusions: Tandem CD19/CD22 dual targets CAR-T cells therapy obtains superior CR rate than single CD19 and sequential CD19/CD22 CAR-T cells therapy. This provides an effective treatment option for R/R B-ALL patients with chemotherapy resistance. Disclosures No relevant conflicts of interest to declare.

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