Setting Appropriate Goals for the Next Generation of Clinical Trials in Myelofibrosis.

New targeted therapies administered in phase II and phase III studies have produced substantial improvements in outcomes of myelofibrosis (MF). However, strong documentation that the new agents modify the natural history of the disease is lacking, and a number of therapeutic indications of new drugs remain unaddressed. Overall survival (OS) improvement is the major goal of next-generation clinical trials in MF. This may be attained if an adequate population of patients and an unambiguous design of the trial will be selected. Another goal is preventing disease progression in early MF: this requires a controlled clinical trial with an accessible endpoint and a clinically relevant definition of disease progression. Improvement in the documentation of responsiveness of patient-reported outcomes (PROs) will allow to use them as a critical endpoint of new trials. Finally, exploiting the clinical utility of biomarkers should become a major goal of future clinical experimentation in MF.