An analytical biomarker for treatment of patients with recurrent B-ALL after remission induced by infusion of anti-CD19 chimeric antigen receptor T (CAR-T) cells

Zhang, Wenying; Dai, Hanren; Wang, Yao; Shi, Fengxia; Wang, Chunmeng; Guo, Yelei; Liu, Yang; Chen, Meixia; Feng, Kang; Zhang, Yan; Liu, Chuanjie; Yang, Qingming; Li, Suxia; Han, Weidong

doi:10.1007/s11427-016-5035-4

Cited by 17 publications

(11 citation statements)

References 31 publications

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“…Following deduplication and screening by title/abstract and full manuscript, a total of 42 hematologic cancer studies (775 patients) and 18 solid cancer studies (138 patients) met our full eligibility criteria (Fig 1). Following screening and de-duplication, there were eight studies that reported patient data that was fully duplicated [5,[16][17][18][19][20][21][22] and two studies partially duplicated [23,24].…”

Section: Resultsmentioning

confidence: 99%

Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis

Grigor

Fergusson

Kekre

et al. 2019

Transfusion Medicine Reviews

150

122

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Promising efficacy results of chimeric antigen receptor (CAR) T-cell therapy have been tempered by safety considerations. Our objective was to comprehensively summarize the efficacy and safety of CAR-T cell therapy in patients with relapsed or refractory hematologic or solid malignancies. MEDLINE, Embase, and the Cochrane Register of Controlled Trials (inception -November 21, 2017). Interventional studies investigating CAR-T cell therapy in patients with malignancies were included. Our primary outcome of interest was complete response (defined as the absence of detectable cancer). Two independent reviewers extracted relevant data, assessed risk of bias, and graded the quality of evidence using established methods. A total of 42 hematological malignancy studies and 18 solid tumor studies met were included (913 participants). Of 486 evaluable hematologic patients, 54.4% [95% CI, 42.5%-65.9%] experienced complete response in 27 CD19 CAR-T cell therapy studies. Of 65 evaluable hematologic patients, 24.4% [95% CI, 9.4%-50.3%] experienced complete response in seven non-CD19 CAR-T cell therapy studies. Cytokine release syndrome was experienced by 55.3% [95% CI, 40.3%-69.4%] of patients and neurotoxicity 37.2% [95% CI, 28.6%-46.8%] of patients with hematologic malignancies. Of 86 evaluable solid tumor patients, 4.1% [95% CI, 1.6%-10.6%] experienced complete response in eight CAR-T cell therapy studies. Limitations include heterogeneity of study populations, as well as high risk of bias of included studies. There was a strong signal for efficacy of CAR-T cell therapy in patients with CD19+ hematologic malignancies and no overall signal in solid tumor trials published to date. These results will help inform patients, physicians, and other stakeholders of the benefits and risks associated with CAR-T cell therapy. (M.M. Lalu). @manojlalu (M.M. Lalu).

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Section: Resultsmentioning

confidence: 99%

Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis

Grigor

Fergusson

Kekre

et al. 2019

Transfusion Medicine Reviews

150

122

View full text Add to dashboard Cite

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“…[ 36 – 41 ]. In addition, some serum biochemical markers, including C-reactive protein (CRP) and ferritin levels are always elevated in patients who experienced CRS after CAR-T cell therapy [ 13 , 28 – 30 , 37 , 42 , 43 ]. Monitoring the changes of those laboratory markers after CAR-T cell infusion can give insight in to CRS, and investigational cytokine activation profiles that are associated with CRS have been documented in several CAR-T clinical trials [ 4 , 13 , 29 ].…”

Section: Manifestations Of Crs Related To Car-t Cell Therapymentioning

confidence: 99%

Biomarkers of cytokine release syndrome and neurotoxicity related to CAR-T cell therapy

2018

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Severe cytokine release syndrome (CRS) and neurotoxicity following chimeric antigen receptor T cell (CAR-T) therapy can be life-threatening in some cases, and management of those toxicities is still a great challenge for physicians. Researchers hope to understand the pathophysiology of CRS and neurotoxicity, and identify predictive biomarkers that can forecast those toxicities in advance. Some risk factors for severe CRS and/or neurotoxicity including patient and treatment characteristics have been identified in multiple clinical trials of CAR-T cell therapy. Moreover, several groups have identified some predictive biomarkers that are able to determine beforehand which patients may suffer severe CRS and/or neurotoxicity during CAR-T cell therapy, facilitating testing of early intervention strategies for those toxicities. However, further studies are needed to better understand the biology and related risk factors for CRS and/or neurotoxicity, and determine if those identified predictors can be extrapolated to other series. Herein, we review the pathophysiology of CRS and neurotoxicity, and summarize the progress of predictive biomarkers to improve CAR-T cell therapy in cancer.

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“…It is reported that anti-CD19 CAR-T therapy is beneficial for certain extramedullary tissues relapse with or without allogeneic-HSCT, such as breast, kidney, CNS, pancreas, pelvic fascia, subcutaneous adipose tissue of chest, bone, liver, lung, and muscle tissue. 19 – 23 Herein, we reported a case of an adult patient receiving CD19+ CAR T-cell therapy to treat the relapse of Ph-positive ALL after allogeneic HSCT with an extremely rare location in the cervix, which has never been reported. After the failure of chemotherapy and TKI treatment, the patient underwent CD19+ CAR T-cell therapy and has acquired 8-month full recovery until now with significantly remission of cervix tumor growth and improved life quality.…”

Section: Discussionmentioning

confidence: 99%

Extramedullary relapse of acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation treated by CAR T-cell therapy: a case report

Wang

Shi

Wang³

et al. 2018

OTT

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Philadelphia chromosome-positive (Ph-positive) acute leukemia (ALL) accounts for around one quarter of adult cases of ALL and is usually associated with poor prognosis. The patients still encounter a high rate of relapse even after they receive hematopoietic stem cell transplantation (HSCT). HSCT is considered the established therapy and best option for many malignant ALL cases, however, disease relapse remains the main reason of failure. In recent years, chimeric antigen receptor (CAR) T-cell therapy has become a promising treatment for patients with advanced blood cancers. Here, we report a rare case of a Ph-positive ALL patient with extramedullary relapse in her cervix after receiving allogeneic HSCT. Given the unsatisfactory response to chemotherapy, tyrosine kinase inhibitor (TKI) treatment, and HSCT transplantation, she had received CD19+ CAR T-cell therapy 8 months earlier. The following ultrasound check indicated that her cervix relapse went through significant remission with almost undetectable tumor mass. This case strongly supports the efficacy of CAR T-cell therapy on adult ALL with extramedullary relapse.

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An analytical biomarker for treatment of patients with recurrent B-ALL after remission induced by infusion of anti-CD19 chimeric antigen receptor T (CAR-T) cells

Cited by 17 publications

References 31 publications

Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis

Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis

Biomarkers of cytokine release syndrome and neurotoxicity related to CAR-T cell therapy

Extramedullary relapse of acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation treated by CAR T-cell therapy: a case report

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