COMBINED VALPROIC ACID THERAPY FOR ACUTE MYELOID LEUKEMIA IN OLDER PATIENTS: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Long Cheng^{1, #}, Shenglin Wang^{2, #}, Xiaomi Ding², Mingyue Chen², Feng Tang², Wei Wei³, Jing Zhou², Guohui Jiang^{2, *}

¹Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China - ²Department of Neurology, Affiliated Hospital of North Sichuan Medical College; Institute of neurological diseases, North Sichuan Medical College, Nanchong, Sichuan, China - ³Medical Information Consulting Service, Sichuan Provincial Health Policy & Medical Information Institute, Chengdu, Sichuan, China

Background: Currently, there is still no consensus regarding the optimal management for acute myeloid leukemia (AML) in older patients. Valproic acid (VPA), as a potent histone deacetylase (HDAC) inhibitor and antiepileptic agent, has proved to cause differentiation and apoptosis in hematopoietic malignancies. But the combination of potent histone deacetylase (HDAC) inhibitors with other drugs remains controversial. Our meta-analysis of randomized controlled trials (RCTs) systematically evaluates the clinical effectiveness and safety of VPA combined with other drugs in the treatment of elder patients in AML to provide an evidence-based reference for clinical practice.

Methods: PubMed, Embase, Web of Science, Cochrane were searched by four investigators from inception to January 2020. Three RCTs were included in the meta-analyses. A random-effects model was employed for analysis. Subgroup analysis stratified by the all-trans retinoic acid (ARTA) schedule was performed to investigate the potential sources of heterogeneity.

Findings: Statistical analysis showed no statistical difference was found in the complete remission (CR) and toxicity of VPA in combination with other drugs.

Interpretation: The addition of VPA to the therapeutic regimen is not associated with improved outcomes in the treatment of elderly AML, which can guide clinical medication and avoid unreasonable medication. Future therapies may consider combining more stronger HDAC inhibitors and exploring new effective therapy for older AML patients.