1. Combination of dasatinib and venetoclax in newly diagnosed chronic phase chronic myeloid leukemia.
- Author
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Jabbour E, Haddad FG, Sasaki K, Carter BZ, Alvarado Y, Nasnas C, Nasr L, Masarova L, Daver N, Pemmaraju N, Short NJ, Skinner J, Kadia T, Borthakur G, Garcia-Manero G, Ravandi F, Issa GC, Andreeff M, and Kantarjian H
- Subjects
- Humans, Middle Aged, Adult, Female, Aged, Male, Young Adult, Leukemia, Myeloid, Chronic-Phase drug therapy, Leukemia, Myeloid, Chronic-Phase genetics, Dasatinib administration & dosage, Dasatinib therapeutic use, Dasatinib adverse effects, Bridged Bicyclo Compounds, Heterocyclic administration & dosage, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Bridged Bicyclo Compounds, Heterocyclic adverse effects, Sulfonamides administration & dosage, Sulfonamides therapeutic use, Sulfonamides adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use
- Abstract
Background: The dual inhibition of the BCR::ABL1 tyrosine kinase and BCL-2 could potentially deepen the response rates of chronic myeloid leukemia in chronic phase (CML-CP). This study evaluated the safety and efficacy of the combination of dasatinib and venetoclax., Methods: In this phase 2 trial, patients with CML-CP or accelerated phase (clonal evolution) received dasatinib 50 mg/day for three courses; venetoclax was added in course 4 for 3 years. The initial venetoclax dose was 200 mg/day continuously but reduced later to 200 mg/day for 14 days, and to 100 mg/day for 7 days per course once a molecular response (MR)4.5 was achieved. After 3 years of combination, patients were maintained on single-agent dasatinib. The primary end point was the rate of major molecular response (MMR) by 12 months of combination., Results: Sixty-five patients were treated. Their median age was 46 years (range, 23-73). By 12 months of combination, the MMR, MR4, and MR4.5 rates were 86%, 53%, and 45%, respectively. After a median follow-up of 42 months, the 4-year event-free and overall survival rates were 96% and 100%, respectively. Outcomes with the combination were comparable to historical outcomes with single-agent dasatinib (cumulative 12-months MMR rate of 79% with both strategies). The incidence of grade 3-4 neutropenia was 22% with the combination and 11% with single-agent dasatinib (p < .001)., Conclusions: Treatment with dasatinib and venetoclax was safe and effective in CML-CP. The cumulative response rates with the combination were similar to those with single-agent dasatinib. Further follow-up is needed to evaluate the rates of durable deep molecular response and treatment-free remission., (© 2024 American Cancer Society.)
- Published
- 2024
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