Clinical Epidemiology in Contemporary Patients With Myelofibrosis.

Myeloproliferative neoplasms (MPNs) are rare bone marrow disorders characterized by clonal proliferation of hematopoietic cell lineages, and include polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). MF has worse prognosis, with main causes of death including acute leukemia transformation, comorbid conditions, and consequences of cytopenia. MF is characterized by progressive anemia, bone marrow fibrosis, and extramedullary hematopoiesis with splenomegaly. Moreover, the disease is associated with a heavy symptom burden including night sweats, fever, bone pain, and weight loss and worsening the quality of life.

On the beginning of 2013 the European Registry for Myeloproliferative Neoplasms (ERNEST) observational study was launched and approved by several IRBs of European hematological centers. The study focused on overt Primary (PMF) and Secondary myelofibrosis (SMF; i.e., post-Essential Thrombocythemia myelofibrosis (post-ET MF) and post-polycythemia (post-PV MF)) and aimed at describing the clinical epidemiology of large series of patients observed in clinical practice. This research was justified as the landscape of both pathophysiological and clinical knowledge in MPNs was rapidly evolving, prompting to revise diagnostic criteria, prognostication and therapy recommendations.

ERNEST retrospectively enrolled 1292 patients in whom the proposed prognostic models were confirmed to differentiate treatments in clinical practice, while ERNEST-2 reported results on critical events observed in 1010 of these cases during a median follow-up period of 5.4 years.4,5 The two studies closed in December 2022.

In the last decade, new diagnostic and prognostic findings have been accumulated and the availability of new approved drugs, based on results of several new clinical trials, influenced the therapy decision making in the real-world clinical practice. Therefore, the continuation of observational studies in present ERNEST-3 on large multicenter case series of patients with MF is timely and might refine the results of clinical trials.

The purpose of this study observational retrospective/prospective study is to gain information on MF associated cytopenias that represent a significant challenge in the contemporary patients with MF. Currently, there are few agents aimed at treating cytopenic MF, including immunomodulatory drugs, hypomethylating agents, and JAK inhibitors such as momelotinib and pacritinib, and development of new agents specifically tailored to this patient population remains an unmet need. Therefore, this study can provide data on these patients, focusing on clinical status, quality of life, comorbidities, and treatment results over time.

• Frequency and types of cytopenias [Time frame: At baseline; 1 year follow-up.]
• Treatments response and duration (according to modified IWG-MRT and ELN 2013 criteria, overall and by presence of cytopenias [Time frame: At baseline; 1 year follow-up.]
• Incidence of major CV events (thrombosis and bleeding), overall and by presence of cytopenias and treatments received [Time frame: At baseline; 1 year follow-up.]
• Incidence of disease progressions (MF accelerated phase, MF blast phase/acute myeloid leukemia (AML)), overall and by presence of cytopenias and treatments received [Time frame: At baseline; 1 year follow-up.]
• Incidence of secondary neoplasia, overall, by site and by presence of cytopenias and treatments received [Time frame: At baseline; 1 year follow-up.]
• Incidence of infections, overall and by presence of cytopenias and treatments received [Time frame: At baseline; 1 year follow-up.]
• Incidence of adverse events (AEs) of interest, overall, by type, severity and treatments received [Time frame: At baseline; 1 year follow-up.]
• Incidence of death, overall, by cause and by presence of cytopenias and treatments received [Time frame: At baseline; 1 year follow-up.]