BRAF Inhibition Effective for Hairy-Cell Leukemia

Treatment with a short course of vemurafenib, a BRAF inhibitor, was effective and rapid in patients with relapsed or refractory hairy-cell leukemia, resulting in overall response rates of greater than 95%, according to the results of two phase II studies.

“In these two trials involving patients with hairy-cell leukemia, an oral course of vemurafenib (at a dose of 960 mg twice daily for 16 to 18 weeks) was rapidly and highly effective, with response rates of 96% in the Italian study and 100% in the US study and with low-grade toxic effects in patients who not only were heavily pretreated but often had disease that was refractory to their last therapy,” wrote Brunangelo Falini, MD, of the University of Perugia, and colleagues in the New England Journal of Medicine.

Falini and colleagues conducted phase II single-group studies of vemurafenib 960 mg in the United States and in Italy. Therapy was given for a median of 16 weeks in the Italian study and 18 weeks in the US study. The primary endpoints were complete response rate (Italian trial) and overall response rate (US trial).

“Rather than administering vemurafenib for an indefinite duration, as is done in patients with metastatic melanoma, we limited the initial vemurafenib treatment to a few months (even if this perhaps reduced the type or duration of response) owing to concern about vemurafenib induced secondary tumors,” the researchers explained.

In the Italian study, the overall response rate was 96% after a median of 8 weeks with a complete response rate of 35%. At a median follow-up of 23 months, the median relapse-free survival was 19 months among those patients with a complete response. Among patients with a partial response, median relapse-free survival was 6 months. Median treatment-free survival was 25 months and 18 months among these two groups respectively.

In the US trial, the overall response rate was 100% after a median of 12 weeks and the complete response rate was 42%. At 1 year, the progression-free survival rate was 73% with an overall survival rate of 91%.

“A longer duration of treatment did not appear to improve the type or duration of the response,” the researchers wrote. “Retreatment with vemurafenib at the time of relapse was effective in the two trials, although to a lesser extent in the patients who had a relapse after a partial response than in those who had a relapse after a complete response in the Italian study.”

According to the study, the most common adverse events, typically grade 1 or 2, were toxic events of the skin, arthralgia or arthritis, pyrexia, and elevated bilirubin level. Seven of 50 patients developed secondary cutaneous tumors.

To evaluate the use of vemurafenib further in this patient population, Felini and colleagues recommended a study of BRAF inhibitors in combination with anti-CD20 monoclonal antibodies or with MEK inhibitors.