Dataset Information

Biomarkers for Chimeric Antigen Receptor T Cell Therapy in Acute Lymphoblastic Leukemia: Prospects for Personalized Management and Prognostic Prediction.

ABSTRACT: Chimeric antigen receptor (CAR) T cell therapy represents a breakthrough in immunotherapy with the potential of ushering in a new era in cancer treatment. Remarkable therapeutic response and complete remission of this innovative management have been observed in patients with relapse/refractory acute lymphoblastic leukemia. With CAR-T cell therapy becoming widely used both in multicenter clinical trials and as a commercial treatment, therapeutic efficacy monitoring and management of toxicities will be indispensable for ensuring safety and improving overall survival. Biomarkers can act not only as effective indicators reflecting patients' baseline characteristics, CAR-T cell potency, and the immune microenvironment, but can also assess side effects during treatment. In this review, we will elaborate on a series of biomarkers associated with therapeutic response as well as treatment-related toxicities, and present their current condition and latent value with respect to the clinical utility. The combination of biomarker research and CAR-T cell therapy will contribute to establishing a safer and more powerful monitoring system and prolonging the event-free survival of patients.

SUBMITTER: Hong R

PROVIDER: S-EPMC7947199 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Biomarkers for Chimeric Antigen Receptor T Cell Therapy in Acute Lymphoblastic Leukemia: Prospects for Personalized Management and Prognostic Prediction.

Hong Ruimin R Hu Yongxian Y Huang He H

Frontiers in immunology 20210225

Chimeric antigen receptor (CAR) T cell therapy represents a breakthrough in immunotherapy with the potential of ushering in a new era in cancer treatment. Remarkable therapeutic response and complete remission of this innovative management have been observed in patients with relapse/refractory acute lymphoblastic leukemia. With CAR-T cell therapy becoming widely used both in multicenter clinical trials and as a commercial treatment, therapeutic efficacy monitoring and management of toxicities wi ...[more]

PMID: 33717147

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Project description:ObjectiveInitial success with chimeric antigen receptor-modified T cell therapy for relapsed/refractory acute lymphoblastic leukemia is leading to expanded use through multicenter trials. Cytokine release syndrome, the most severe toxicity, presents a novel critical illness syndrome with limited data regarding diagnosis, prognosis, and therapy. We sought to characterize the timing, severity, and intensive care management of cytokine release syndrome after chimeric antigen receptor-modified T cell therapy.DesignRetrospective cohort study.SettingAcademic children's hospital.PatientsThirty-nine subjects with relapsed/refractory acute lymphoblastic leukemia treated with chimeric antigen receptor-modified T cell therapy on a phase I/IIa clinical trial (ClinicalTrials.gov number NCT01626495).InterventionsAll subjects received chimeric antigen receptor-modified T cell therapy. Thirteen subjects with cardiovascular dysfunction were treated with the interleukin-6 receptor antibody tocilizumab.Measurements and main resultsEighteen subjects (46%) developed grade 3-4 cytokine release syndrome, with prolonged fever (median, 6.5 d), hyperferritinemia (median peak ferritin, 60,214 ng/mL), and organ dysfunction. Fourteen (36%) developed cardiovascular dysfunction treated with vasoactive infusions a median of 5 days after T cell therapy. Six (15%) developed acute respiratory failure treated with invasive mechanical ventilation a median of 6 days after T cell therapy; five met criteria for acute respiratory distress syndrome. Encephalopathy, hepatic, and renal dysfunction manifested later than cardiovascular and respiratory dysfunction. Subjects had a median of 15 organ dysfunction days (interquartile range, 8-20). Treatment with tocilizumab in 13 subjects resulted in rapid defervescence (median, 4 hr) and clinical improvement.ConclusionsGrade 3-4 cytokine release syndrome occurred in 46% of patients following T cell therapy for relapsed/refractory acute lymphoblastic leukemia. Clinicians should be aware of expanding use of this breakthrough therapy and implications for critical care units in cancer centers.

Dataset Information

Biomarkers for Chimeric Antigen Receptor T Cell Therapy in Acute Lymphoblastic Leukemia: Prospects for Personalized Management and Prognostic Prediction.

Publications

Biomarkers for Chimeric Antigen Receptor T Cell Therapy in Acute Lymphoblastic Leukemia: Prospects for Personalized Management and Prognostic Prediction.

Similar Datasets

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