INHIBITOR OF B-RAFV600E MUTATION AS A TREATMENT OPTION FOR HAIRY CELL LEUKEMIA WITH DEEP NEUTROPENIA AND INFECTIOUS COMPLICATIONS

Abstract Background The use of standard therapy in HCL is often impossible at the time of deep neutropenia/agranulocytosis with or without infectious complications thus it is a complex therapeutic problem. Vemurafenib has been used to treat resistant HCL since 2012. As vemurafenib doesn’t have a myelotoxic effect, we considered, that it can be used in the therapy of HCL in deep neutropenia/agranulocytosis with or without the development of infectious complications as a preliminary stage before treatment with cladribine. We conducted a retrospective analysis of treatment with vemurafenib of 22 patients in deep neutropenia/agranulocytosis with or without infectious complications at the diagnosis, followed by the standard course of cladribine. Patients and methods Vemurafenib was used in 22 patients with HCL. The response to therapy was evaluated by a complete blood cell count test (the absolute neutrophils count (ANC), hemoglobin concentration, platelets count, the absence of "hairy" cells), spleen size (with ultrasound examination), and reduce infectious complications. After there one standard course of the cladribine was used. Results Among the 22 patients, the ratio of men and female was 2:1; median age was 52 years (24-78 years), there were 7 patients with severe infectious manifestations admitted to the intensive care unit including 1 patient – during extracorporeal membrane oxygenation. The median of ANC at the diagnosis was 0.3 х 109/l (0.04 – 0.7 х 109/l). Vemurafenib was used in a dose of 240 mg 1-2 times a day. In 20 patients, vemurafenib was used for 3 months or more. In one case, the effect was not obtained during 1 month of treatment and the patient died from severe infectious complications during prolonged agranulocytosis. In 21 patients treated with vermurafenib, an increase of ANC was observed and the infectious complications were resolved, therefore allowing the application of cladribine therapy. After 1 standard course (0.1 mg/kg/day x 7 days) of cladribine chemotherapy, 18 (90%) patients achieved complete clinical remission and 2 (10%) patients achieved partial remission with residual splenomegaly. In 1 patient, vemurafenib therapy is currently ongoing (2 months from the start of therapy). Conclusion In cases with proven BRAFV600E mutation vemurafenib can be successfully used as an effective preliminary therapy in patients with deep neutropenia/agranulocytosis with or without infectious complications before standard therapy with purine analogs.