Preclinical and Case Series Studies on the Combination of Venetoclax with Epigenetic Drugs in T-Cell Acute Lymphoblastic Leukemia
Year: 2025
Type: article
Abstract: Boyue Zheng,1,* Jiyi Fu,1,* Yijing Wang,2 Jiafei Wu,1 Jun Wang,3 Hui Li1,4 1School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Hematology, Chengdu Fifth People’s Hospital, Chengdu, People’s Republic of China; 3Department of Hematology, Chengdu Second People’s Hospital, Chengdu, People’s Republic of China; 4Department of Hematology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Li, Email [email protected]: Adult T-cell acute lymphoblastic leukemia (T-ALL) exhibits a dismal prognosis characterized by low remission rates, high relapse rates, and poor tolerance to conventional chemotherapy. The urgent development of novel therapeutic strategies is imperative to improve clinical outcomes. In this study, we propose a dual epigenetic targeting regimen combining Venetoclax with Chidamide and Azacitidine. Preclinical investigations demonstrated synergistic anti-proliferative effects of this triple-drug combination against Jurkat cells in vitro. Additionally, we retrospectively analyzed clinical data from five high-risk T-ALL patients to evaluate the regimen’s efficacy and safety. Among the cohort (all male; median age 55 years, range 25– 72), one patient had refractory T-ALL (R-TALL) following VDCP regimen induction failure, while four were newly diagnosed (ND-TALL). After one treatment cycle, four patients achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi), with one additional patient attaining CR after the second cycle. Four patients achieved deep molecular remission (MRD-negative status) within two cycles, while two successfully underwent allogeneic hematopoietic stem cell transplantation (HSCT) during sustained remission. Myelosuppression emerged as the predominant treatment-related adverse event. These preclinical and clinical findings collectively support the therapeutic potential of the Combination of Venetoclax with Epigenetic Drugs as a promising option for high-risk T-ALL patients.Keywords: acute T-lymphoblastic leukemia, epigenetics, chidamide, venetoclax, efficacy, safety
Authors: Zheng B, Fu J, Wang Y, Wu J, Wang J, Li H
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7103601874
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