Rapid Response of Biallelic BRAF V600E Hairy Cell Leukaemia to Low Dose Vemurafenib

Abstract 4890 Following the recent report that identified the V600E BRAF mutation in Hairy Cell Leukaemia (HCL) (Tiacci et al NEJM 2011), we confirmed this finding in 48/48 patients diagnosed with HCL in the Cambridge Haematology Laboratory (Boyd et al BJHaem 2011). One of these patients was found to have a bialleleic V600E BRAF mutation on a bone marrow biopsy taken in 2008. Retrospective molecular analysis of diagnostic material from 1996 confirmed this patient9s disease was heterozygous for BRAF V600E at presentation. He initially enjoyed a long period of disease stability following splenectomy and cladribine in 1996/1997. He was retreated with 6 cycles of cladribine in 2008 but within 3 years he relapsed again and was treated with 6 cycles of pentostatin and rituximab completing in 2011. He achieved a partial bone marrow remission with recovery of normal peripheral blood counts, but his disease progressed within 6 months. He became profoundly cytopenic with circulating hairy cells and was platelet/red cell transfusion dependent. He was intolerant of interferon-alpha. Following the recent report of the successful treatment of a single patient with a BRAF inhibitor (Dietrich et al NEJM 2012), our patient was treated with vemurafenib at a continuous dose of 240mg BD. Pretreatment Day -7 bloods confirmed total white cell count 20.0 × 10 9 /L, neutrophils 0.8 × 10 9 /l, haemoglobin 9.5 g/dl (supported) and platelets 11 × 10 9 /l (supported). In the 3 months prior to starting vemurafenib, he had received 14 units of red cells, 9 transfusions of platelets and on-going G-CSF therapy. Baseline MRI of pelvis and femora revealed diffusely abnormal homogenous bone marrow signal with increased T2 fat suppressed (T2fs) signal and decreased T1 signal Treatment was tolerated with no discernable side effects to date and renal and liver function remained normal on therapy. Flow cytometry quantification confirmed a rapid reduction in peripheral blood hairy cells from pre treatment 19 x10 9 /l, to 3 x10 9 /l by day 7 and 0.002 x10 9 /l on day 36. The final platelet transfusion was on day 15 and platelet counts increased to 37 × 10 9 /l by day 29 and 94 × 10 9 /l by day 36. The last red cell transfusion was on Day 22 and on day 36 the patient9s haemoglobin was 9.4 g/dl. G-CSF was stopped on day 28. The bone marrow remained inaspirable on day 16, but a trephine biopsy revealed early response with some regeneration of normal haematopoiesis. Bone marrow from Day 36 confirmed ongoing haematopoietic recovery but hairy cells persisted. MRI on day 32 showed development of patchy marrow signal throughout consistent with multifocal recovery of haematopoietic marrow. The patient continues on vemurafenib 240mg BD and follow-up data will be presented. Disclosures: Off Label Use: Oral BRAF inhibitor.