Long-term outcomes in patients with relapsed or refractory hairy cell leukemia treated with vemurafenib monotherapy

Hairy cell leukemia (HCL) is a rare chronic B cell lymphoproliferative disorder characterized by high prevalence of BRAF V600E mutation.1,2 Purine nucleoside analogues can achieve an overall response rate (ORR) of 90 to 100% and complete responses (CR) of 80 to 95% and remain the mainstay of first-line treatment in HCL.3,4 However, approximately 30-40% patients will experience recurrent disease and relapse-free survival rates decrease with repeated courses of purine analogue-based treatments with cumulative myelotoxicity and immune suppression.5,6 The genetic basis of HCL was first uncovered a decade ago when Tiacci and colleagues reported that BRAF V600E is a key mutation in HCL,7 a finding that was further validated by subsequent studies.8,9 Based on these findings, we conducted a multicenter phase 2 clinical trial in the U.S. evaluating the efficacy and safety of vemurafenib, an oral BRAF inhibitor, in patients with relapsed/ refractory (R/R) HCL. We previously published the initial outcome of 26 U.S. patients together with the Italian study conducted by Tiacci et al.7 Vemurafenib monotherapy induced 96-100% ORR and 35-42% CR rates in both studies. With a median follow-up duration of 11.7 months, we observed relapses in 29% of the patients but the long-term clinical outcome and response or acquired resistance to vemurafenib retreatment have not been previously reported. Herein, we report the long-term follow-up data of the entire patient cohort in the completed U.S. clinical trial (NCT01711632) including the ORR, relapse free survival, clinical factors associated with improved survival as well as outcomes after retreatment with vemurafenib or alternative agents.