IBCL-341: Inhibitor of B-RAFV600E Mutation in Hairy Cell Leukemia

Abstract

Context: The use of standard therapy (ST) in hairy cell leukemia (HCL) is often impossible at the time of deep neutropenia (DN) or the development of infectious complications (IC). HCL patients who do not respond to ST present a special therapeutic problem. Objective: Vemurafenib has been used to treat resistant HCL since 2012. Vemurafenib does not have a myelotoxic effect and so can be used in therapy of HCL with DN, as well as in early relapse after ST or as a primary refractory course of HCL (RR). Design: The applicability of vemurafenib in patients with HCL with DN, including patients with IC and RR. Setting: Study setting can be used in hematological inpatient (including intensive care department) and outpatient departments. Patients: Vemurafenib was used in 27 patients with HCL (m: f = 2.4; median age 57 years (24–78 years): six RR patients and 21 patients with DN, including 7 patients with severe infectious manifestations in the intensive care department, including 1 patient on extracorporeal membrane oxygenation. Intervention: Vemurafenib was used in a dose of 240 mg 1–2 times a day. In 26 patients, vemurafenib was used for 3 months or more. Main Outcomes Measures: The response to therapy was evaluated by control of neutrophil count, size of the spleen, and resolution of the IC. Results: In patients with DN, the response was achieved in 95%, followed by 1 course of ST with cladribine. In 1 patient, within 1 month of vemurafenib therapy, the effect was not obtained. Among RR patients, 67% achieved remission of the disease after a course of therapy with vemurafenib for 3 months, followed by a ST of cladribine and maintenance therapy with rituximab or obinutuzumab. There were no complications with the use of vemurafenib. Short agranulocytosis within three days after the course of cladribine was observed in only two patients. Conclusion: Therapy of HCL patients with DN, IC, and RR is a complex therapeutic problem. In cases with proven BRAFV600E mutation, vemurafenib can be effectively used not only in RR patients but as an effective preliminary therapy in patients with DN and IN before a ST with purine analogues.