Vemurafenib (Zelboraf), which is already approved for treating advanced melanoma, is now showing considerable promise in treating patients with relapsed or refractory hairy cell leukemia.
Vemurafenib (Zelboraf), which is already approved for treating advanced melanoma, is now showing considerable promise in treating patients with relapsed or refractory hairy cell leukemia. Two, single-group, multicenter studies have found that a short oral course of vemurafenib may be highly effective in patients with relapsed or refractory hairy cell leukemia.
The study was recently published online in The New England Journal of Medicine.1
Enrico Tiacci, MD, and colleagues conducted two separate studies. One included 26 patients in Italy and the other included 24 patients in the United States. The researchers assessed the safety and activity of this oral BRAF inhibitor in patients with hairy cell leukemia who had relapsed after treatment with a purine analogue, or who had disease that was refractory to purine analogues.
The oral agent was administered for a median of 16 weeks in the Italian study and even longer in the US study (18 weeks). The primary endpoints were different in the two studies. In the US trial, the primary endpoint was the overall response rate, but in the Italian trial, the primary endpoint was complete response rate. Vemurafenib works by targeting a mutated form of BRAF, and studies have shown that BRAF is altered in virtually all cases of hairy cell leukemia.
In the Italian study, the researchers found that in 25 out of 26 patients evaluated, the overall response rates were 96% after a median of 8 weeks. The numbers were even better in the US study where investigators reported that 24 out of 24 evaluated patients responded after a median of 12 weeks. Complete responses were found in 9 out of 26 patients (35%) in the Italian study and in 10 out of 24 patients in the US trial (42%).
In the Italian trial, the median relapse-free survival was 19 months among patients with a complete response and 6 months among those with a partial response after a median follow-up of 23 months.
Among these patients in the Italian study, the median treatment-free survival was 25 months for the complete responders and 18 months for the partial responders. In the US trial, the numbers were very promising and the progression-free survival (PFS) rate was 73%, and the overall survival (OS) rate was 91% at 1 year.
The researchers found that the agent was fairly well tolerated and the most common cause leading to dose reductions were grade 1 and 2 rash and arthralgia or arthritis. The investigators also reported that secondary cutaneous tumors developed in 7 of 50 patients, but they were all easily managed.
Vemurafenib reportedly interrupts the B-Raf/MEK step on the B-Raf/MEK/ERK pathway. The researchers write, “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.”1