Combination of venetoclax with BCR-ABL tyrosine kinase inhibitor as a therapeutic strategy for Philadelphia chromosome-positive leukemias
Jing-Ying Zou,
Si-Man Huang,
Hai-Xia Zhoub,
Ming-Zhu Xu,
Ai-Ning Sun,
De-Pei Wu,
Sheng-Li Xue,
Tong-Tong Zhang
Affiliations
Jing-Ying Zou
Suzhou Vocational Health College, Suzhou, People’s Republic of China
Si-Man Huang
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
Hai-Xia Zhoub
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
Ming-Zhu Xu
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
Ai-Ning Sun
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
De-Pei Wu
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
Sheng-Li Xue
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
Tong-Tong Zhang
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
ABSTRACTObjectives: Venetoclax has shown synergism with BCR-ABL1 tyrosine kinase inhibitors (TKIs) in preclinical studies for patients with Philadelphia chromosome-positive (Ph+) leukemias. This combination may suggest a novel treatment strategy for Ph + leukemias.Methods: We conducted a retrospective study to summarize the activity of combining venetoclax and BCR-ABL1 TKI-based therapies in Ph + leukemias.Result: A total of 18 patients with Ph + leukemias were enrolled in this study. At the time of venetoclax and TKI-based therapy, 5 patients were initially diagnosed, with Ph + acute myeloid leukemia (AML) (n = 1) and mixed phenotype acute leukemia (MPAL) (n = 4), 7 patients had chronic myeloid leukemia at blastic phase (CML-BP), and the remaining 6 patients had relapsed or refractory to prior therapy. The overall response rate (ORR) was 88.9% (9 CR, 2 CRi, 4 MLFS, 1 PR), and a major molecular response (MMR) (or better) was achieved in 7 (38.8%) of all patients. With a median follow-up of 7.0 months (range, 2.3-15.6), 15 (83.3%) were in continuous CR at the time of this analysis, with a 1-year OS of 85.6%, 1-year LFS of 76.7%, and 1-year CIR of 22.4%. Moreover, 10 of 18 patients were treated with venetoclax, TKI and hypomethylating agent (HMA) regimens, which also associated with a high ORR rate (6 CR, 1 CRi, 3 MLFS), and can be used for induction or salvage therapy.Conclusion: Venetoclax and TKI-based combination regimens may be a feasible approach for Ph + leukemias, and prospective studies are needed to properly assess the safety, tolerability and efficacy of this regimen.
