Venetoclax in Previously Treated Waldenström Macroglobulinemia
Autor: | Christopher J. Patterson, Lian Xu, Tanya Siddiqi, Maria Luisa Guerrera, Shayna Sarosiek, Zachary R. Hunter, Andrew R. Branagan, Xia Liu, Carly Leventoff, Catherine A Flynn, Ranjana H. Advani, Kirsten Meid, Nicholas Tsakmaklis, Maria Demos, Matthew S. Davids, Guang Yang, Amanda Kofides, Timothy P White, Manit Munshi, Steven P. Treon, Jorge J. Castillo, Richard R. Furman, John N. Allan |
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Rok vydání: | 2023 |
Předmět: |
Adult
Male Cancer Research Receptors CXCR4 Time Factors Antineoplastic Agents chemistry.chemical_compound Biomarkers Tumor Medicine Humans Prospective Studies BCL2 ANTAGONIST Aged Aged 80 and over Sulfonamides Venetoclax business.industry Waldenstrom macroglobulinemia Middle Aged medicine.disease Bridged Bicyclo Compounds Heterocyclic Progression-Free Survival United States Oncology chemistry Proto-Oncogene Proteins c-bcl-2 Mutation Myeloid Differentiation Factor 88 Cancer research Disease Progression Female Waldenstrom Macroglobulinemia Previously treated business |
Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 40(1) |
ISSN: | 1527-7755 |
Popis: | PURPOSE BCL2 is overexpressed and confers prosurvival signaling in malignant lymphoplasmacytic cells in Waldenström macroglobulinemia (WM). Venetoclax is a potent BCL2 antagonist and triggers in vitro apoptosis of WM cells. The activity of venetoclax in WM remains to be clarified. PATIENTS AND METHODS We performed a multicenter, prospective phase II study of venetoclax in patients with previously treated WM ( NCT02677324 ). Venetoclax was dose-escalated from 200 mg to a maximum dose of 800 mg daily for up to 2 years. RESULTS Thirty-two patients were evaluable, including 16 previously exposed to Bruton tyrosine kinase inhibitors (BTKis). All patients were MYD88 L265P–mutated, and 17 carried CXCR4 mutations. The median time to minor and major responses was 1.9 and 5.1 months, respectively. Previous exposure to BTKis was associated with a longer time to response (4.5 v 1.4 months; P < .001). The overall, major, and very good partial response rates were 84%, 81%, and 19%, respectively. The major response rate was lower in those with refractory versus relapsed disease (50% v 95%; P = .007). The median follow-up time was 33 months, and the median progression-free survival was 30 months. CXCR4 mutations did not affect treatment response or progression-free survival. The only recurring grade ≥ 3 treatment-related adverse event was neutropenia (n = 14; 45%), including one episode of febrile neutropenia. Laboratory tumor lysis without clinical sequelae occurred in one patient. No deaths have occurred. CONCLUSION Venetoclax is safe and highly active in patients with previously treated WM, including those who previously received BTKis. CXCR4 mutation status did not affect treatment response. |
Databáze: | OpenAIRE |
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