EJHaem · 2025
NOTCH1 Mutation Is Associated With Response to Bruton Tyrosine Kinase Inhibitors in Chronic Lymphocytic Leukemia: A Retrospective Study.
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Haméon Clémence, Houot Roch, Gyan Emmanuel, Vallet Nicolas, Lachot Sébastien, Ganard Michel, Herault Olivier, De Guibert Sophie, Pastoret Cédric, Dartigeas Caroline
Аннотация
BACKGROUND: Chronic lymphocytic leukemia (CLL) treatment choice remains a challenge in the era of molecular biology and targeted therapy.
METHODS: We conducted a bicentric retrospective analysis of the impact of NOTCH1 mutation according to the treatment of CLL patients in real life.
RESULTS: A total of 45 patients with NOTCH1 mutation have been reported, including 15 patients treated with FCR BR or DRC regimen and 18 patients with a BTK inhibitor. NOTCH1 mutation is the most frequently occurring molecular abnormality in CLL and is closely associated with poor prognosis but is not used in treatment guidelines unlike TP53 and IGHV. In our study, progression-free survival was significantly longer in CLL patients with NOTCH1 mutation treated by BTK inhibitors compared to immunochemotherapy.
CONCLUSION: Routine screening for NOTCH1 mutations could identify patients who may benefit from BTKi treatment. However, the impact of NOTCH1 mutations on combination therapies, such as obinutuzumab-venetoclax or venetoclax-BTKi, is yet to be determined.The authors have confirmed clinical trial registration is not needed for this submission.
METHODS: We conducted a bicentric retrospective analysis of the impact of NOTCH1 mutation according to the treatment of CLL patients in real life.
RESULTS: A total of 45 patients with NOTCH1 mutation have been reported, including 15 patients treated with FCR BR or DRC regimen and 18 patients with a BTK inhibitor. NOTCH1 mutation is the most frequently occurring molecular abnormality in CLL and is closely associated with poor prognosis but is not used in treatment guidelines unlike TP53 and IGHV. In our study, progression-free survival was significantly longer in CLL patients with NOTCH1 mutation treated by BTK inhibitors compared to immunochemotherapy.
CONCLUSION: Routine screening for NOTCH1 mutations could identify patients who may benefit from BTKi treatment. However, the impact of NOTCH1 mutations on combination therapies, such as obinutuzumab-venetoclax or venetoclax-BTKi, is yet to be determined.The authors have confirmed clinical trial registration is not needed for this submission.