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XPO1 Mutation in CLL: Prevalence and Prognostic Value

By: Kayci Reyer
Posted: Tuesday, December 15, 2020

Research published in the British Journal of Haematology found XPO1 mutation in patients with chronic lymphocytic leukemia (CLL) appeared to be more prevalent than in other large-scale studies. Fanny Baran-Marszak, MD, PhD, of the Institut National de la Santé et de la Recherche Médicale in France, and colleagues also found that patients who have XPO1 mutation may experience comparable survival and disease progression outcomes as those who do not.

The study included 246 patients with progressive CLL, 152 of whom had progressive disease and 94 of whom had relapsed or refractory disease. The median patient age was 60.2 years. All patients underwent IGHV sequencing, next-generation sequencing, fluorescence in situ hybridization analysis, and conventional cytogenetics. Five patients who had XPO1 mutation also underwent longitudinal analysis. The IGHV status was unmutated for 157 participants (64%), mutated for 87 participants (35%), and unavailable for 2 participants (1%).

The occurrence rate of XPO1 mutation was relatively high at 8% (n = 19), and a relationship was noted between XPO1 mutation and unmutated IGHV status—18 of 19 patients with XPO1 mutation had an unmutated IGHV status. Among those with XPO1 mutation, 6 patients (32%) had no other alteration, whereas 13 patients had variable associations with TP53, SF3B1, NOTCH1, BIRC3, ATM, or FBXW7 mutations. The time to first treatment, event-free survival, and overall survival was similar for patients with and without XPO1 mutation.

The co-occurrence of XPO1 and TP53 mutations were rare, occurring in just three patients overall. Of note, two of the five patients with XPO1 mutation who underwent longitudinal analysis experienced post-treatment onset of TP53 mutation. The authors believe this may suggest TP53 alteration might develop at a later point in the disease and may be independently targetable.

Disclosure: The study authors reported no conflicts of interest.



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