scholarly journals Chimeric Antigen Receptor T-cell (CAR T) Therapy for Hematologic and Solid Malignancies: Efficacy and Safety—A Systematic Review with Meta-Analysis

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 47 ◽  
Author(s):  
Wen-Liang Yu ◽  
Zi-Chun Hua
Keyword(s):  
T Cells ◽  
Response Rate ◽  
Meta Analysis ◽  
Complete Response ◽  
Hematologic Malignancies ◽  
Common Side Effect ◽  
Future Research ◽  
Efficacy And Safety ◽  
Tumor Patients ◽  
Car T

Chimeric antigen receptors T cells (CAR T) had been used for treating various tumor patients in clinic, and owned an incredible efficacy in part of malignancies. However, CAR T therapy remains controversial due to doubts about its efficacy and safety in the clinical treatment of various malignancies. A total of 997 tumor patients from 52 studies were included in this review. Eligible studies were searched and reviewed from the databases of PubMed, Web of Science, Wanfang and Clinicaltrials.gov. Then meta-analysis and subgroup analysis were used to investigate the overall response rate (ORR), complete response rate (CRR), common side effect rate (CSER) and relapse rate (RR) of CAR T therapy for patients in clinical researches, respectively. The results further confirmed that CAR T therapy had a higher response rate for hematologic malignancies. More importantly, CAR T therapy had a higher CSER in patients with hematologic malignancies, and it had a similar RR in patients with different malignancies. Cell cultured without the addition of IL-2 and total administration less than 108 cells were recommended. This study offers a reference for future research regarding the application in solid and hematologic malignancies, side effects and relapse, and even the production processes of CAR T cells.

scholarly journals Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Jun Meng ◽  
XiaoQin Wu ◽  
Zhen Sun ◽  
RenDe Xun ◽  
MengSi Liu ◽  
...  
Keyword(s):  
T Cell ◽  
Response Rate ◽  
Complete Response ◽  
Hematologic Malignancies ◽  
Efficacy And Safety ◽  
Real World Data ◽  
Immune Effector ◽  
Car T Cell ◽  
Car T ◽  
Life Threatening

BackgroundCurrently, three chimeric antigen receptor (CAR)-T cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel have been approved by the U.S. Food and Drug Administration for the treatment of large B cell lymphoma, which provide a novel and promising choice for patients with relapsed or refractory to traditional anti-tumor treatments. Thus, it is pertinent to describe the efficacy and safety profile of the three products available by summarizing the current evidence.MethodsTwo reviewers independently searched the Embase, PubMed, Web of Science, and Cochrane Library, to identify studies related to the use of the three CAR-T cell products for treating hematologic malignancies published up to October 5, 2020. We pooled the overall response rate, complete response rate, cytokine release syndrome, and immune effector cell-associated neurotoxicity syndrome of three products, and then performed subgroup analysis based on the type of product and type of tumor.ResultsThirty-three studies involving 2,172 patients were included in the analysis. All three products showed promising results in patients with different pathological subtypes and clinical characteristics that included those who did not meet the eligibility criteria of licensing trials, with overall response rates of nearly 70% or above and complete response rates of more than 50%. However, high rates of severe immune effector cell-associated neurotoxicity syndrome in patients undergoing axicabtagene ciloleucel treatment and life-threatening cytokine release syndrome in patients with leukemia undergoing tisagenlecleucel treatment required special attention in practice (31%; 95% CI: 0.27–0.35 and 55%; 95% CI: 0.45–0.64, respectively). Moreover, lisocabtagene maraleucel that showed a favorable efficacy and safety in the licensing trial lacked corresponding real-world data.ConclusionBoth axicabtagene ciloleucel and tisagenlecleucel showed considerable efficacy in practice, but need special attention with respect to life-threatening toxicity that can occur in certain situations. Lisocabtagene maraleucel demonstrated excellent efficacy and safety profiles in the licensing trial, but lacked corresponding real-world data. Additional data on the three products are needed in rare histological subtypes to benefit a broader patient population.

Adoptive Immunotherapy for B-cell Malignancies Using CD19- Targeted Chimeric Antigen Receptor T-Cells: A Systematic Review of Efficacy and Safety

2019 ◽  
Vol 26 (17) ◽  
pp. 3068-3079 ◽  
Author(s):  
Lu Hao ◽  
Tongtong Li ◽  
Lung-Ji Chang ◽  
Xiaochuan Chen
Keyword(s):  
Renal Failure ◽  
T Cells ◽  
Acute Renal Failure ◽  
Complete Remission ◽  
Adverse Effects ◽  
B Cell ◽  
Meta Analysis ◽  
Efficacy And Safety ◽  
B Cell Malignancies ◽  
Car T

Background:Adoptive infusion of chimeric antigen receptor transduced T- cells (CAR-T) is a powerful tool of immunotherapy for hematological malignancies, as evidenced by recently published and unpublished clinical results.Objective:In this report, we performed a meta-analysis to evaluate the efficacy and side effects of CAR-T on refractory and/or relapsed B-cell malignancies, including leukemia and lymphoma.Methods:Clinical studies investigating efficacy and safety of CAR-T in acute and chronic lymphocytic leukemia and lymphoma were identified by searching PubMed and EMBASE. Outcomes of efficacy subjected to analysis were the rates of complete remission (CR) and partial remission (PR). The safety parameters were the prevalence of adverse effects including fever, hypotension, and acute renal failure. Meta analyses were performed using R software. Weighted hazard ratio (HR) with 95% confidence intervals was calculated for each outcome. Fixed or random-effects models were employed depending on the heterogeneity across the included studies.Results:Nineteen published clinical studies with a total of 391 patients were included for the meta-analysis. The pooled rate of complete remission was 55% (95% CI 41%-69%); the pooled rate of partial remission was 25% (95% CI: 19%-33%). The prevalence of fever was 62% (95% CI: 41%-79%), the hypotension was 22% (95% CI: 15%-31%), and the acute renal failure was 24% (95% CI: 16%-34%). All adverse effects were manageable and no death was reported due to toxicity.Conclusion:CD19-targeted CAR-T is an effective modality in treating refractory B-cell malignancies including leukemia and lymphoma. However, there is still a need to develop strategies to improve the safety in its clinical use.

scholarly journals Efficacy and Safety of Eculizumab in the Treatment of Transplant-Associated Thrombotic Microangiopathy: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Rui Zhang ◽  
Meng Zhou ◽  
Jiaqian Qi ◽  
Wenjing Miao ◽  
Ziyan Zhang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Thrombotic Microangiopathy ◽  
Response Rate ◽  
Meta Analysis ◽  
Complete Response ◽  
Current Evidence ◽  
Efficacy And Safety ◽  
Impaired Liver Function ◽  
Hematopoietic Stem ◽  
Impaired Liver

BackgroundTransplant-associated thrombotic microangiopathy (TA-TMA) is a dangerous and life-threatening complication in patients undergoing hematopoietic stem cell transplantation (HSCT). Eculizumab has been used in the treatment of TA-TMA, and several studies have confirmed the benefit of Eculizumab in patients with TA-TMA. However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Eculizumab for TA-TMA.Materials and MethodsWe searched PubMed and Embase for studies on the efficacy and safety of Eculizumab in TA-TMA patients. Efficacy outcomes consisted of overall response rate (ORR), complete response rate (CRR), and survival rate at the last follow-up (SR). Safety outcomes were adverse events (AEs), including infection, sepsis, impaired liver function, infusion reactions, and death.ResultsA total of 116 patients from six studies were subjected to meta-analysis. The pooled estimates of ORR, CRR, and SR for TA-TMA patients were 71% (95% CI: 58–82%), 32% (95% CI: 11–56%), and 52% (95% CI: 40–65%), respectively. Only one patient presented with a severe rash, and infection was the most common AEs. The main causes of death were infection and GvHD.ConclusionCurrent evidence suggests that Eculizumab improves SR and ORR in patients with TA-TMA and that Eculizumab is well tolerated. However, the number of studies is limited, and the findings are based mainly on data from observational studies. Higher quality randomized controlled trials and more extensive prospective cohort studies are needed.

scholarly journals Investigating the Efficacy and Safety of Thalidomide for Treating Patients With ß-Thalassemia: A Meta-Analysis

2022 ◽  
Vol 12 ◽  
Author(s):  
Yanfei Lu ◽  
Zhenbin Wei ◽  
Gaohui Yang ◽  
Yongrong Lai ◽  
Rongrong Liu
Keyword(s):  
Blood Transfusion ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Overall Response Rate ◽  
Response Rate ◽  
Complete Response Rate ◽  
Meta Analysis ◽  
Globin Gene ◽  
Complete Response ◽  
Efficacy And Safety

At present, the main therapies for ß-thalassemia patients include regular blood transfusion and iron chelation, associating with a number of limitations. Thalidomide, a fetal hemoglobin (HbF) inducer that promotes γ-globin gene expression, has been reported to be effective for ß-thalassemia. Thus, this meta-analysis was conducted to assess the efficacy and safety of thalidomide for treating patients with ß-thalassemia. We searched the related studies from eight databases published from inception until December 1, 2021. The R 4.0.5 language programming was used to perform meta-analysis. After screening of retrieved articles, 12 articles were included that enrolled a total of 451 patients. The Cochrane Collaboration risk assessment tool was used to evaluate the quality and the bias risk of the randomized controlled trials (RCTs), and non randomized trials were assessed using Newcastle-Ottawa Scale (NOS). After treatment with thalidomide, the pooled overall response rate (ORR) was 85% (95% confidence interval (CI): 80–90%), and the pooled complete response rate (CRR) was 54% (95% confidence interval: 31–76%). Compared with the placebo group, the thalidomide group had higher odds of overall response rate (odds ratio = 20.4; 95% CI: 6.75–61.64) and complete response rate (odds ratio = 20.4; 95% CI: 6.75–61.64). A statistically significant increase in hemoglobin level and HbF level after treatment, while there was no statistically significant difference in adult hemoglobin (HbA) level, spleen size, and serum ferritin. According to the results of ORR and CRR, transfusion-dependent thalassemia (TDT) patients showed remarkable efficacy of thalidomide, 83 and 52% respectively. So we analyzed 30 transfusion-dependent thalassemia patients from three studies and found that the most frequent ß-globin gene mutations were CD41-42 (-TCTT), while response to thalidomide did not show any statistically significant relationship with XmnI polymorphism or CD41-42 (-TCTT) mutation. About 30% of patients experienced mild adverse effects of thalidomide. Collectively, thalidomide is a relatively safe and effective therapy to reduce the blood transfusion requirements and to increase Hb level in patients with ß-thalassemia.

Chimeric Antigen Receptor-Engineered T-Cells - A New Way and Era for Lymphoma Treatment

2020 ◽  
Vol 14 (4) ◽  
pp. 312-323
Author(s):  
Romeo G. Mihăilă
Keyword(s):  
T Cells ◽  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Car T Cells ◽  
Future Developments ◽  
Car T Cell ◽  
Large B Cell Lymphoma ◽  
Car T

Background: Patients with refractory or relapsed diffuse large B-cell lymphoma have a poor prognosis with the current standard of care. Objective: Chimeric Antigen Receptor T-cells (CAR T-cells) are functionally reprogrammed lymphocytes, which are able to recognize and kill tumor cells. The aim of this study is to make progress in this area. Method: A mini-review was achieved using the articles published in Web of Science and PubMed in the last year and the new patents were made in this field. Results: The responses to CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel are promising; the objective response rate can reach up to 83%, and the complete response rate ranges between 40 and 58%. About half of the patients may have serious side effects, such as cytokine release syndrome and neurotoxicity. Current and future developments include the improvement of CAR T-cell expansion and polyfunctionality, the combined use of CAR T-cells with a fusion protein between interferon and an anti-CD20 monoclonal antibody, with checkpoint inhibitors or small molecule sensitizers that have apoptotic-regulatory effects. Furthermore, the use of IL-12-expressing CAR T-cells, an improved technology for the production of CAR T-cells based on targeted nucleases, the widespread use of allogeneic CAR T-cells or universal CAR T-cells obtained from genetically engineered healthy donor T-cells are future developments actively considered. Conclusion: CAR T-cell therapy significantly improved the outcome of patients with relapsed or refractory diffuse large B-cell lymphoma. The advances in CAR T-cells production technology will improve the results and enable the expansion of this new immunotherapy.

scholarly journals CAR-T cells and BiTEs in solid tumors: challenges and perspectives

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Julien Edeline ◽  
Roch Houot ◽  
Aurélien Marabelle ◽  
Marion Alcantara
Keyword(s):  
T Cells ◽  
Solid Tumors ◽  
Specific Antigen ◽  
Hematologic Malignancies ◽  
Antibody Fragments ◽  
New Drugs ◽  
Car T Cells ◽  
Cell Specificity ◽  
Car T ◽  
Early Phase Clinical Trials

AbstractChimeric antigen receptor (CAR)-modified T cells and BiTEs are both immunotherapies which redirect T cell specificity against a tumor-specific antigen through the use of antibody fragments. They demonstrated remarkable efficacy in B cell hematologic malignancies, thus paving the way for their development in solid tumors. Nonetheless, the use of such new drugs to treat solid tumors is not straightforward. So far, the results from early phase clinical trials are not as impressive as expected but many improvements are under way. In this review we present an overview of the clinical development of CAR-T cells and BiTEs targeting the main antigens expressed by solid tumors. We emphasize the most frequent hurdles encountered by either CAR-T cells or BiTEs, or both, and summarize the strategies that have been proposed to overcome these obstacles.

scholarly journals CAR-T in Cancer Treatment: Develop in Self-Optimization, Win-Win in Cooperation

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1955
Author(s):  
Feifei Guo ◽  
Jiuwei Cui
Keyword(s):  
T Cells ◽  
Cancer Treatment ◽  
Unmet Needs ◽  
Hematologic Malignancies ◽  
Limiting Factors ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell Therapy ◽  
Car T ◽  
Application Prospects

Despite remarkable achievements in the treatment of hematologic malignancies, chimeric antigen receptor (CAR)-T cell therapy still faces many obstacles. The limited antitumor activity and persistence of infused CAR-T cells, especially in solid tumors, are the main limiting factors for CAR-T therapy. Moreover, clinical security and accessibility are important unmet needs for the application of CAR-T therapy. In view of these challenges, many potentially effective solutions have been proposed and confirmed. Both the independent and combined strategies of CAR-T therapy have exhibited good application prospects. Thus, in this review, we have discussed the cutting-edge breakthroughs in CAR-T therapy for cancer treatment, with the aim of providing a reference for addressing the current challenges.

scholarly journals Efficacy and safety of Si-Jun-Zi-Tang-based therapies for functional (non-ulcer) dyspepsia: a meta-analysis of randomized controlled trials

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yaping Wang ◽  
Bin Liu ◽  
Xiuqiong Fu ◽  
Tiejun Tong ◽  
Zhiling Yu
Keyword(s):  
Relapse Rate ◽  
Large Scale ◽  
Primary Outcome ◽  
Response Rate ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Efficacy And Safety ◽  
History Of ◽  
Non Ulcer Dyspepsia

Abstract Background The traditional Chinese medicine formula Si-Jun-Zi-Tang (SJZT) has a long history of application in the treatment of functional dyspepsia (non-ulcer dyspepsia, FD)-like symptoms. SJZT-based therapies have been claimed to be beneficial in managing FD. This study aimed to assess the efficacy and safety of SJZT-based therapies in treating FD by meta-analysis. Methods Systematic searches for RCTs were conducted in seven databases (up to February 2019) without language restrictions. Data were analyzed using Cochrane RevMan software version 5.3.0 and Stata software version 13.1, and reported as relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CIs). The primary outcome was response rate and the secondary outcomes were gastric emptying, quality of life, adverse effects and relapse rate. The quality of evidence was evaluated according to criteria from the Cochrane risk of bias. Results A total of 341 potentially relevant publications were identified, and 12 RCTs were eligible for inclusion. For the response rate, there was a statically significant benefit in favor of SJZT-based therapies (RR = 1.23; 95% CI 1.17 to 1.30). However, the benefit was limited to modified SJZT (MSJZT). The relapse rate of FD patients received SJZT-based therapies was lower than that of patients who received conventional medicines (OR = 0.23; 95% CI 0.10 to 0.51). No SJZT-based therapies-related adverse effect was reported. Conclusion SJZT-based prescriptions may be effective in treating FD and no serious side-effects were identified, but the effect on response rate appeared to be limited to MSJZT. The results should be interpreted with caution as all the included studies were considered at a high risk of bias. Standardized, large-scale and strictly designed RCTs are needed to further validate the benefits of SJZT-based therapies for FD management. Trial registration Systematic review registration: [PROSPERO registration: CRD42019139136].

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.

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