Hairy Cell Leukemia

Vemurafenib plus Rituximab in Refractory or Relapsed Hairy-Cell Leukemia

Vemurafenib plus Rituximab in Refractory or Relapsed Hairy-Cell Leukemia

Background and Purpose

Hairy cell leukemia is an indolent CD20 positive B-cell lymphoma.  The vast majority of cases expressed the BRAF V600E.  This is a kinase activating mutation which plays an important pathologic role in this disease.  The targeting of this protein in hairy cell leukemia has been well reported in other studies, with response rates up to 91% reported.  35% of patients have a complete response.  Importantly, the median relapse free survival has been reported as 9 months after discontinuation of therapy.


A single center, phase 2 academic trial was performed.  Patients were required to have refractory or relapsed hairy cell leukemia.  Safety and efficacy of vemurafenib dosed at 960 mg twice daily for 8 weeks plus concurrent and sequential rituximab 375 mg/m² body surface area, administered for 8 doses over a period of 18 weeks was performed.  The primary endpoint was complete response at the end of the treatment study.


30 patients were enrolled.  The median number of previous therapies was 3.  A complete response was seen in 26 patients, 87% in the intent to treat population.  All patients who had hairy cell leukemia had been refractory to chemotherapy or rituximab. All the patients who had HCL that had been refractory to chemotherapy (n=10 patients) or rituximab (n=5 patients) and all those who had previously been treated with BRAF inhibitors (n=7 patients) had a complete response. Thrombocytopenia resolved after meeting of 2 weeks of neutropenia after meeting to 4 weeks.  Of the 26 patients with a complete response, 65%, 17 patients were cleared of minimal residual disease.  Of the 30 patients, progression free survival was 78% at a median follow-up of 37 months.  Among 26 patients, relapse free survival was 85% at a medium follow-up of 34 months.  Minimal residual disease negativity, and no previous BRAF inhibitor treatment correlated with longer relapse free survival with post hoc analysis.  The majority of side effects were grade 1 or 2.


The authors concluded “in this small study, short, chemotherapy free, nonmyelotoxic regimen of the vemurafenib plus rituximab is associated with a durable complete response in most patients with refractory or relapsed hairy cell leukemia.


Vemurafenib plus Rituximab in Refractory or Relapsed Hairy-Cell Leukemia