BACKGROUND: BRAF V600E is the genetic lesion underlying hairy-cell leukemia. We 
assessed the safety and activity of the oral BRAF inhibitor vemurafenib in 
patients with hairy-cell leukemia that had relapsed after treatment with a 
purine analogue or who had disease that was refractory to purine analogues.
METHODS: We conducted two phase 2, single-group, multicenter studies of 
vemurafenib (at a dose of 960 mg twice daily)--one in Italy and one in the 
United States. The therapy was administered for a median of 16 weeks in the 
Italian study and 18 weeks in the U.S. study. Primary end points were the 
complete response rate (in the Italian trial) and the overall response rate (in 
the U.S. trial). Enrollment was completed (28 patients) in the Italian trial in 
April 2013 and is still open (26 of 36 planned patients) in the U.S. trial.
RESULTS: The overall response rates were 96% (25 of 26 patients who could be 
evaluated) after a median of 8 weeks in the Italian study and 100% (24 of 24) 
after a median of 12 weeks in the U.S. study. The rates of complete response 
were 35% (9 of 26 patients) and 42% (10 of 24) in the two trials, respectively. 
In the Italian trial, after a median follow-up of 23 months, the median 
relapse-free survival was 19 months among patients with a complete response and 
6 months among those with a partial response; the median treatment-free survival 
was 25 months and 18 months, respectively. In the U.S. trial, at 1 year, the 
progression-free survival rate was 73% and the overall survival rate was 91%. 
Drug-related adverse events were usually of grade 1 or 2, and the events most 
frequently leading to dose reductions were rash and arthralgia or arthritis. 
Secondary cutaneous tumors (treated with simple excision) developed in 7 of 50 
patients. The frequent persistence of phosphorylated ERK-positive leukemic cells 
in bone marrow at the end of treatment suggests bypass reactivation of MEK and 
ERK as a resistance mechanism.
CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients 
with relapsed or refractory hairy-cell leukemia. (Funded by the Associazione 
Italiana per la Ricerca sul Cancro and others; EudraCT number, 2011-005487-13; 
ClinicalTrials.gov number NCT01711632.).