Outcomes with chimeric antigen receptor t-cell therapy in relapsed or refractory acute myeloid leukemia: a systematic review and meta-analysis
Topic: Immunotherapy

Background: We conducted a systematic review and meta-analysis to evaluate outcomes following chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory acute myeloid leukemia (RR-AML). Methods: We performed a literature search on PubMed, Cochrane Library, and Clinicaltrials.gov. After screening 677 manuscripts, 13 studies were included. Data was extracted following PRISMA guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed. Results: We analyzed 57 patients from 10 clinical trials and 3 case reports. The pooled complete and overall response rates were 49.5% (95% CI 0.18-0.81, I2 =65%) and 65.2% (95% CI 0.36-0.91, I2 =57%). The pooled incidence of cytokine release syndrome, immune-effector cell associated neurotoxicity syndrome, and graft-versus-host disease was estimated as 54.4% (95% CI 0.17-0.90, I2 =77%), 3.9% (95% CI 0.00-0.19, I2 =22%), and 1.6% (95%CI 0.00-0.21, I2 =33%), respectively. Conclusion: CAR-T therapy has demonstrated modest efficacy in RR-AML. Major challenges include heterogeneous disease biology, lack of a unique targetable antigen, and immune exhaustion.

PICO
Population: Patients with relapsed/refractory acute myeloid leukemia (RR-AML)
Intervention: Chimeric antigen receptor T cell (CAR-T) therapy
Comparison: N/A
Outcomes: Outcomes following CAR-T therapy in RR-AML such as complete and overall response rates, and the incidence of cytokine release syndrome, immune-effector cell associated neurotoxicity syndrome, and graft-versus-host disease

Included studies:
title: Cytotoxic effect of CLL-1 CAR-T cell immunotherapy with PD-1 silencing on relapsed/refractory acute myeloid leukemia
title: Phase I trial of autologous CAR T cells targeting NKG2D ligands in patients with AML/MDS and multiple myeloma
title: First-in-man clinical trial of CAR NK-92 cells: safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia
title: Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia
title: Anti-CLL1 chimeric antigen receptor T-cell therapy in children with Relapsed/Refractory acute myeloid leukemia
title: Phase 1 clinical trial of adoptive immunotherapy using “off-the-shelf” activated natural killer cells in patients with refractory and relapsed acute myeloid leukemia
title: NKG2D-based chimeric antigen receptor therapy induced remission in a relapsed/refractory acute myeloid leukemia patient
title: Proof of concept for a rapidly switchable universal CAR-T platform with UniCAR-T-CD123 in relapsed/refractory AML
title: Donor-derived CD123-targeted CAR T cell serves as a RIC regimen for haploidentical transplantation in a patient with FUS-ERG+ AML
title: CD38-directed CAR-T cell therapy: a novel immunotherapy strategy for relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation
title: Successful treatment of two relapsed/refractory t(8;21) acute myeloid leukemia patients by CD19-directed chimeric antigen receptor T cells.