| Abstract: | Patients with hairy cell leukaemia (HCL ) have highly favourable outcomes after purine analogue therapy. However, most patients subsequently relapse and require re‐treatment. A minority of patients develop purine analogue‐refractory disease. Targeted therapies have improved outcomes for such patients. Recently, the BRAF V600E mutation was identified in most patients with classical HCL , resulting in constitutive mitogen‐activated protein kinase pathway activation; impressive responses are achieved in heavily pre‐treated patients with BRAF inhibition. The CD 22‐targeted immunoconjugate moxetumomab pasudotox and BTK inhibitor ibrutinib also achieve responses in relapsed and refractory patients. HCL variant and the IGHV 4‐34 molecular variant of HCL lack BRAF mutation and have inferior outcomes with standard purine analogue therapy. The addition of rituximab to purine analogues achieves very high rates of minimal residual disease‐negative complete remission and improves outcomes for patients with HCL variant. Given the rarity of HCL , optimal integration of novel therapies into treatment algorithms will require well‐designed, collaborative studies. |
