<p>Survival outcomes and efficacy of autologous CD19 chimeric antigen receptor-T cell therapy in the patient with diagnosed hematological malignancies: a systematic review and meta-analysis</p>

Abstract

Purpose: Chimeric Antigen Receptor T(CAR-T) cell therapy is an immunotherapy approach used in treating cancer which has seen rapid development over the decades. It becomes the preferred treatment choice after patients have failed conventional chemotherapy. Methods: We conducted a meta-analysis in 320 patients from 14 studies to estimate the survival outcome, response rate and toxicity of autologous CD19 CAR-T cell therapy and predict other factors associated with a better prognosis. Results: The overall response rate was 71.88% (95% CI: 61.34–80.46%, p <0.01) and CRS toxicity was 60.15% (95% CI: 42.87–75.22%, p <0.01). Patients who received lymphodepletion was associated with a better response rate (77%, 95%CI: 67–83%; p -value =0.001) in comparison to the other patients who did not (66%, 95%CI: 41–83%). Conclusion: Lymphodepletion regimen may play a crucial role in predicting the prognosis of patients with hematological malignancies. Lymphodepletion patients had better progression-free survival than those who did not.

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

“…Meta-analysis and systematic reviews on the safety and efficacy of CAR-T cell therapy for hematologic and solid malignancies have been published, but a comprehensive evaluation of the three currently marketed CAR-T cell products is lacking (7)(8)(9)(10)(11)(12)(13)(14)(15). In real-world clinical setting, most patients receive only these approved products rather than the experimental CAR-T cells that were mainly focused in the previous studies.…”

The Influence of Chimeric Antigen Receptor Structural Domains on Clinical Outcomes and Associated Toxicities

“…Multiple factors have been reported to impact CD19 CAR-T cell therapy clinical outcome in patients, including whether a patient has received conditioning lymphodepletion therapy prior to CAR-T cell infusion, whether CAR-T cells were cultured with IL-2 prior to infusion and the extent of CAR-T cell persistence in patients [ 52 , 53 ]. For the studies shown in Table 1 , we saw no obvious effect of age, conditioning lymphodepletion treatment or CAR-T cell dosage on patient complete response rate ( Table 2 ).…”

T Cell Activation Machinery: Form and Function in Natural and Engineered Immune Receptors

“…While the FDA approval of two such “second-generation” designs in late 2017 (tisagenlecleucel/Kymriah ® and axicabtagene ciloleucel/Yescarta ® ) for B cell malignancies has kept much of the effort to develop new CAR-T cell therapies focused on similar single-chain designs, many alterations have been investigated that can modulate their performance, and approaches are being developed that seek to improve safety and/or efficacy by incorporating lessons from the now-substantial body of knowledge around natural immune receptor structure, assembly, activation and regulation. The sections that follow are not intended to provide exhaustive coverage of the CAR design space (see detailed recent reviews [ 128 , 129 , 130 , 131 , 132 , 133 , 134 ]), and we will not focus heavily on the large number of completed or ongoing clinical trials (see detailed recent reviews [ 5 , 6 , 135 , 136 ]). Rather, we discuss what is known about single-chain CAR structure and function with reference to the above overview of natural immune receptors, identifying similarities and contrasts to highlight what we view as key benefits and liabilities of different features and domain configurations (summarized in Figure 2 ).…”