A short course of vemurafenib, an oral BRAF inhibitor, was highly effective in patients with relapsed or refractory hairy-cell leukemia, a rare form of lymphocytic leukemia that shares some features with chronic lymphocytic leukemia (CLL), a new study published in The New England Journal of Medicine has shown.1
Because BRAF V600E is the underlying genetic mutation that drives hairy-cell leukemia, researchers sought to evaluate the activity and safety of vemurafenib in patients with relapsed or refractory disease by conducting 2 phase 2 studies, one in the United States and another in Italy.
For the studies, researchers enrolled 28 patients with hairy-cell leukemia that had relapsed after treatment with a purine analogue or who had disease that was refractory to purine analogues in the Italian trial and 26 of 36 planned patients in the US trial.
All patients received vemurafenib 960 mg orally twice daily for a median of 16 weeks in the Italian study and 18 weeks in the US trial.
Results showed that the overall response rates were 96% and 100% among evaluable patients after a median of 8 weeks and 12 weeks in the Italian trial and the US trial, respectively.
Researchers found that 35% and 42% of patients in the Italian trial and the US trial, respectively, achieved a complete response. One-year progression free survival rate was 73% and 1-year overall survival rate was 91% in the US study.
In regard to safety, the most common vemurafenib-associated adverse events leading to dose reductions with rash and arthralgia, but most side effects were grade 1 or 2.
The study also demonstrated that bypass reactivation of MEK and ERK may be a resistance mechanism for vemurafenib in this patient population.
- Tiacci E, Park JH, De Carolis L, et al. Targeting mutant BRAF in relapsed or refractory hairy-cell leukemia. N Engl J Med. 2015; 373(18):1733-1747.