Venetoclax combined with olverembatinib and prednisone as a frontline therapeutic strategy for Philadelphia chromosome-positive mixed-phenotype acute leukemia.

Mixed-phenotype acute leukemia (MPAL) is a rare hematological malignancy with poor prognosis, for which there are currently no standardized therapeutic guidelines. Preclinical and clinical studies have shown that venetoclax and BCR::ABL1 tyrosine kinase inhibitors have synergistic effects on Philadelphia chromosome-positive (Ph +) leukemias. We retrospectively analyzed five patients with de novo Ph + MPAL who received venetoclax, olverembatinib, and prednisone (VOP) therapy. All patients achieved complete remission after the initial induction therapy and tested negative for measurable residual disease. During consolidation therapy, two patients developed severe myelosuppression and died of respiratory failure due to pulmonary infections. The remaining three patients underwent allogeneic hematopoietic stem cell transplantation and maintained durable complete molecular remission. These findings suggest that the VOP regimen may be effective in patients with Ph + MPAL. However, they also underscore the need to optimize venetoclax dosing during consolidation to reduce the risk of life-threatening myelosuppression and infectious complications.