March 21, 2014Blood
Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial
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Discussion
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Implication
Randomized trial demonstrates that TP53, SF3B1, and NOTCH1 mutations predict survival and response to chemoimmunotherapy in chronic lymphocytic leukemia, indicating markers for therapy selection.
Key Points
- To evaluate the prognostic and predictive impact of TP53, NOTCH1, and SF3B1 gene mutations on treatment response and survival in patients with previously untreated chronic lymphocytic leukemia.
- Analyzed TP53, NOTCH1, and SF3B1 mutational status among untreated chronic lymphocytic leukemia patients enrolled in the randomized CLL8 trial (NCT00281918).
- Compared first-line treatment regimens of fludarabine and cyclophosphamide (FC) versus FC combined with rituximab (FCR).
- Conducted multivariable and predictive marker analyses for progression-free survival (PFS) and overall survival (OS).
- Mutations in TP53, NOTCH1, and SF3B1 occurred in 11.5%, 10.0%, and 18.4% of patients, respectively; NOTCH1 and SF3B1 mutations were almost mutually exclusive (0.6% concurrence).
- Multivariable analysis identified TP53 and SF3B1 mutations as independent adverse prognostic factors for progression-free survival, while TP53 mutation independently impaired overall survival.
- NOTCH1 mutation served as a predictive biomarker, with the addition of rituximab failing to improve response or survival in patients harboring NOTCH1 mutations.
Cite This Study
Stilgenbauer et al. (2014) studied this question.