[Efficacy and safety analysis of venetoclax in combination with multidrug chemotherapy in patients with newly diagnosed acute leukemia of ambiguous lineage].

Abstract

Objective: To evaluate the efficacy and safety of venetoclax in combination with multidrug chemotherapy in patients with newly diagnosed acute leukemia of ambiguous lineage (ALAL) . Methods: A retrospective analysis of clinical data was performed on patients with newly diagnosed ALAL who were hospitalized at Jiangsu Provincial People's Hospital from June 2021 to July 2024. Of the 13 patients who received initial induction therapy with venetoclax combined with multidrug chemotherapy, 8 received VAA+P regimen, and 5 received V+IA regimen. Patients with FLT3 mutation were treated with FLT3 inhibitor, and Ph(+) patients received an additional tyrosine kinase inhibitor. Overall survival (OS), disease-free survival (DFS), and adverse events were analyzed. Results: According to the World Health Organization 5th edition of the classification of hematolymphoid tumors, the immunophenotypes were T/myeloid mixed-phenotype acute leukemia (MPAL) (n=4), B/myeloid MPAL (n=7), and ALAL- not otherwise specified (n=2). Of the seven patients with B/myeloid MPAL, four were Ph(+) and belonged to the group with specific gene abnormalities of ALAL. Three patients had FLT3 mutation (one with FLT3-TKD mutation and two with FLT3-ITD mutation). Prior to the second course of consolidation therapy, the efficacy of venetoclax induction therapy was evaluated, and a complete response rate of 100% was achieved in 13 patients. In the subsequent consolidation therapy phase, one patient discontinued treatment and was lost to follow-up; nine patients underwent allogeneic hematopoietic stem cell transplantation, four of whom died due to posttransplant complications and five achieved DFS. Of the three patients (≥70 years old) who received consolidation therapy as before, two achieved DFS and one died due to central nervous system leukemia. The median OS time was not reached in 13 patients; the 75th percentile survival time was 12.0 months, with a 12-month cumulative survival rate of 64.5%. The median DFS time was not reached in all patients; the 75th percentile DFS time was 8.2 months, with a 12-month cumulative DFS rate of 67.1%. All patients experienced grade 3 or 4 hematologic toxicity, including neutropenia and thrombocytopenia, during and after induction therapy. All patients recovered hematopoietic function after the initial induction therapy, with no fatal hemorrhage, tumor lysis syndrome, neurological adverse events, or grade 3 or higher organ toxicity, excluding preexisting conditions. Conclusion: Venetoclax in combination with multidrug chemotherapy was effective and associated with tolerable adverse reactions in patients with newly diagnosed ALAL.