Hairy cell leukemia (HCL) and HCL-like disorders: present, emergent treatment options and future directions

IntroductionHairy cell leukemia accounts for less than 2% of leukemias. The hairy cells express CD11c, CD25, CD103, and CD123 markers. The BRAFV600E mutation was detected in 95% of HCL cases. Patients achieve high complete response rate with purine analogues with or without rituximab, but relapses are inevitable. HCL-like disorders including HCL variant, splenic diffuse red pulp lymphoma, and splenic marginal zone lymphoma are BRAFV600E negative. The CD25 expression is negative. The absence of BRAFV600E mutation in HCL variant contrasts with the presence of mitogen-activated protein kinase kinase 1 (MAP2K1) mutations in 50% of cases.Areas coveredWe investigated the criteria used to distinguish HCL from HCL-like disorders. Recent discoveries in molecular biology have enabled the introduction of several new drugs in HCL patients. We explore the investigational agents: inhibitors of BRAF, MEK, and Bruton tyrosine kinase and potential future strategies we will use in the future in patients with relapsed/refractory HCL. We also discuss the clinical trials in progress.Expert opinionThe association of Cladribine (CDA) with rituximab (R) is the standard first-line treatment in fit HCL and HCL variant patients. BRAF and BTK inhibitors are options in relapsed/refractory HCL patients. The optimal treatment sequences remain to be determined.