Venetoclax Plus Chidamide/Azacitidine Dual Epigenetic Target Regimen in High-Risk Acute Lymphoblastic Leukemia: Preclinical and Case Series Studies

Adult T-ALL has a poor prognosis, with traditional chemotherapy showing low remission rates, high relapse rates, and poor tolerance. There is an urgent need for new treatment regimens to improve the prognosis of T-ALL patients. We propose a dual epigenetic target regimen combining venetoclax with chidamide/azacitidine. Through preclinical studies, we explored whether the combination of these three drugs has a synergistic inhibitory effect on the proliferation of Jurkat cells and retrospectively analyzed the clinical data of four T-ALL patients to preliminarily explore the efficacy and safety of this regimen. The vitro experiments demonstrated that the combination of venetoclax, chidamide, and azacitidine had a synergistic inhibitory effect on the proliferation of Jurkat cells. The study included four male patients with a median age of 40.5 years (25.3, 57.3), all with high-risk factors. One patient had refractory T-ALL (R T-ALL) that failed induction with the VDCP regimen, and three patients had newly diagnosed T-ALL (ND T-ALL). Bone marrow immunophenotyping indicated one case of Pro-T, one case of Pre-T, one case of ETP-ALL, and one case of MPAL (T/My). One patient had chromosomal abnormalities, three had gene mutations, one had a mediastinal mass, three had lymphadenopathy, and none had central nervous system involvement. Three patients achieved CR/CRi after one cycle of the regimen, and one patient achieved CR after the second cycle. Three patients achieved deep remission and MRD negativity after two cycles. Two patients underwent hematopoietic stem cell transplantation after achieving CR and are currently in sustained remission, being dynamically followed up in the outpatient clinic. The most common adverse reaction during treatment was myelosuppression. Both preclinical study conclusions and clinical research data support the venetoclax plus chidamide/azacitidine dual epigenetic target regimen as a preferred treatment option for high-risk T-ALL patients.