ROP-ET: a prospective phase III trial investigating the efficacy and safety of ropeginterferon alfa-2b in essential thrombocythemia patients with limited treatment options.

Interferon-based therapies, such as ropeginterferon alfa-2b have emerged as promising disease-modifying agents for myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET). Current ET treatments aim to normalize hematological parameters and reduce the thrombotic risk, but they do not modify the natural history of the disease and hence, have no impact on disease progression. Ropeginterferon alfa-2b (trade name BESREMi®), a novel, monopegylated interferon alfa-2b with an extended administration interval, has demonstrated a robust and sustained efficacy in polycythemia vera (PV) patients. Given the similarities in disease pathophysiology and treatment goals, ropeginterferon alfa-2b holds promise as a treatment option for ET. The ROP-ET trial is a prospective, multicenter, single-arm phase III study that includes patients with ET who are intolerant or resistant to, and/or are ineligible for current therapies, such as hydroxyurea (HU), anagrelide (ANA), busulfan (BUS) and pipobroman, leaving these patients with limited treatment options. The primary endpoint is a composite response of hematologic parameters and disease-related symptoms, according to modified European LeukemiaNet (ELN) criteria. Secondary endpoints include improvements in symptoms and quality of life, molecular response and the safety profile of ropeginterferon alfa-2b. Over a 3-year period the trial assesses longer term outcomes, particularly the effects on allele burden and clinical outcomes, such as disease-related symptoms, vascular events and disease progression. No prospective clinical trial data exist for ropeginterferon alfa-2b in the planned ET study population and this study will provide new findings that may contribute to advancing the treatment landscape for ET patients with limited alternatives. TRIAL REGISTRATION: EU Clinical Trials Register; EudraCT, 2023-505160-12-00; Registered on October 30, 2023.

Treatment of refractory hairy cell leukemia with a BRAF-inhibitor: lessons to be learnt.

Hairy cell leukemia is a rare chronic lymphoproliferative disorder with indolent but progressive clinical course. Patients require treatment when they have significant cytopenia or recurrent infections. The gold standard treatment are purine nucleoside analogues (cladribine and pentostatine), with these agents the rate of complete remission can approach even 95 %. The differential diagnosis between classical hairy cell leukemia and other, rare splenic lymphomas that can mimic this disease might be really challenging. Splenic lymphoma with villous lymphocytes and other new, provisional WHO entities share some, but not all immunophenotypical features with hairy cell leukemia. The correct diagnosis is of an extreme importance as these entities require different treatment. Thus further investigation in the pathogenesis of hairy cell leukemia is required in order to solve this challenge. Discovery of the BRAF V600E mutation as a disease-defining genetic event in hairy cell leukemia can be helpful in both differential diagnosis and treatment of this disease. We report the case of three hairy cell leukemia patients, whose diagnosis or treatment was based on this newly discovered somatic mutation, but the treatment results and side effects were individual.