Rituximab-Vemurafenib Combination for the Treatment of Relapsed/Refractory Hairy Cell Leukemia

Objective: The management of R/R-HCL is not standardized yet. Patients with HCL universally harbor BRAF mutations, which makes BRAF inhibitors a potential treatment approach. The efficacy and safety of the BRAF inhibitor Vemurafenib were evaluated both as a single-agent option in two phase 2 trials and also combined with Rituximab in another phase 2 trial. Patients: We have decided to present the first two consecutive patients who achieved a rapid and prolonged response, relapsing after treatment with purine analogues. The first two patients who received a combination of R-V for R/R HCL from the records of our institutional CLPD registry were reported. Interventions: Rituximab was given intravenously for a total of four injections every two weeks starting simultaneously with Vemurafenib, which was initially started with a total daily dose of 960 and decreased after 2 months up to a minimum of 240 mg/day. Main outcome measures: The efficacy of the combination treatment of R-V was assessed according to the count recovery in first 2 months and bone marrow findings at the end of 6th month. Results: The first patient was a 56-year-old male who had experienced three relapses, all treated with purine analogues. The second patient was a 33-year-old male who had a refractory disorder after administration of Cladribine. Both patients have achieved a complete count recovery in the first two months and were free of the disease regarding the bone marrow findings achieved at the end of the sixth month. Rituximab and Vemurafenib were all tolerated well with no documented infectious complications. The only dose-limiting complication reported was grade 2 maculo-papular skin rash, which could be managed with a short-term drug holiday and re-institution of Vemurafenib with a reduced dose of 240 mg per event. Conclusions: According to our experience, Rituximab and Vemurafenib combination offers a safe and possibly cost-effective therapeutic option with easily managed treatment emergent adverse events.