No Loose Ends: A Review of the Pharmacotherapy of Hairy Cell and Hairy Cell Leukemia Variant

Objective: To review the literature for the treatment of classical and variant hairy cell leukemia (HCL, HCLv), evaluating efficacy, safety, and supportive care involved in the use of purine analogues (PAs), interferon, BRAF inhibitors, monoclonal antibodies, Bruton's tyrosine kinase inhibitors, and new immunotoxin, moxetumomab pasudotox-tdfk (MPT). An electronic literature search of PubMed (January 1958 to January 2019) was conducted in PubMed using the MESH terms hairy cell leukemia, hairy cell leukemia variant, cladribine, pentostatin, rituximab, interferon, vemurafenib, moxetumomab pasudotox. Study Selection and Data Extraction: Studies written in the English language were considered for this article. The significance of each article was determined by authors independently. Data Synthesis: HCL and HCLv are rare B-cell lymphoproliferative disorders, each with distinct biologies. Symptoms are characterized by pancytopenia and splenomegaly. Initial treatments for HCL were suboptimal, leading to minimal and transient remissions. PAs significantly improved outcomes, inducing remission in most patients. However, those with purine-resistant disease were left with a dearth of options, leading to implementation of vemurafenib for BRAF V600 mutated disease and chemoimmunotherapy with rituximab. Despite these advances, some HCL and a majority of HCLv patients experience relapse. Newer targeted agents offer promise for relapsed and refractory patients, including the recently approved MPT. Relevance to Patient Care and Clinical Practice: This review provides a comprehensive update on the pharmacological management of HCL and HCLv for clinicians who encounter patients with this rare disease. Conclusion: HCL and HCLv are uncommon lymphoid neoplasms that lead to a characteristic constellation of symptoms. The emergence of PAs and novel targeted agents have improved the likelihood and durability of responses for these patients.