Hairy-cell leukemia (HCL) is a rare indolent B-cell neoplasm that responds very well to chemotherapy with purine analogs (cladribine and pentostatin), but relapses are frequent (up to 58% in younger patients) [1, 2] and progressively less sensitive to these myelotoxic and immunesuppressive drugs. Our discovery that the BRAF-V600E mutation is the genetic lesion underlying HCL [3–5] and shaping the morphologic, molecular and anti-apoptotic features of leukemic cells [6], opened the way to BRAF inhibition as targeted therapeutic strategy in this disease [7, 8]. Thus, we and others assessed the safety and efficacy of a short course of vemurafenib (an oral BRAF inhibitor clinically effective in BRAF-V600E + melanoma [9]) delivered to 50 evaluable relapsed/refractory HCL patients enrolled in two phase-2 clinical trials [10]. Vemurafenib (given for a median of 16 or 18 weeks) produced 96–100% overall responses (ORs) and 35–42% complete responses (CRs), all with measurable residual disease (MRD) [10]. In our trial with longer follow-up, the median survival free from relapse of cytopenias in the 25 patients reaching an OR was 9 months after the end of treatment [10].
Safety and efficacy of the BRAF inhibitor dabrafenib in relapsed or refractory hairy cell leukemia: a pilot phase-2 clinical trial
Tiacci E.;De Carolis L.;Merluzzi M.;Perriello V. M.;Santi A.;Venanzi A.;Schiavoni G.;Tasselli L.;Falini B.
2021
Abstract
Hairy-cell leukemia (HCL) is a rare indolent B-cell neoplasm that responds very well to chemotherapy with purine analogs (cladribine and pentostatin), but relapses are frequent (up to 58% in younger patients) [1, 2] and progressively less sensitive to these myelotoxic and immunesuppressive drugs. Our discovery that the BRAF-V600E mutation is the genetic lesion underlying HCL [3–5] and shaping the morphologic, molecular and anti-apoptotic features of leukemic cells [6], opened the way to BRAF inhibition as targeted therapeutic strategy in this disease [7, 8]. Thus, we and others assessed the safety and efficacy of a short course of vemurafenib (an oral BRAF inhibitor clinically effective in BRAF-V600E + melanoma [9]) delivered to 50 evaluable relapsed/refractory HCL patients enrolled in two phase-2 clinical trials [10]. Vemurafenib (given for a median of 16 or 18 weeks) produced 96–100% overall responses (ORs) and 35–42% complete responses (CRs), all with measurable residual disease (MRD) [10]. In our trial with longer follow-up, the median survival free from relapse of cytopenias in the 25 patients reaching an OR was 9 months after the end of treatment [10].I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
