Threading through the data for chemotherapy-free alternatives in the treatment of hairy cell leukemia

Hairy cell leukemia (HCL) is a rare, indolent lymphoproliferative disorder that is highly responsive to purine analog therapy. While agents such as cladribine and pentostatin remain standard front-line therapies, their long-term toxicities-particularly myelosuppression and immune dysfunction-have led to growing interest in chemotherapy-free agents. Recent advances in molecular characterization of HCL, including the near-universal presence of BRAF V600E mutations, have led to an era of targeted therapeutics for the treatment of this disease. In this review, we summarize existing and emerging treatment strategies for HCL, including BRAF and MEK inhibitors, Bruton tyrosine kinase (BTK) inhibitors, anti-CD20 monoclonal antibodies, and venetoclax. These approaches offer therapeutic promise for patients with relapsed/refractory disease and for those ineligible to receive traditional chemotherapy. These regimens also result in high rates of minimal residual disease (MRD) negativity, potentially bringing us closer to the cure for HCL.