Quantitative Analysis of Bone Marrow Features Highlights Heterogeneity in Myelofibrosis Patients Treated with Zinpentraxin Alfa in a Phase II Clinical Study

Quantitative image analysis has potential to transform the interpretation of bone marrow trephine (BMT) samples in myeloproliferative neoplasms (MPN) and improve the evaluation of anti-fibrotic therapies. To investigate the utility of recently developed algorithms evaluating reticulin fibrosis and megakaryocyte features in myelofibrosis (MF), we analysed samples from a multi-center, phase II study of zinpentraxin alfa (ZPN, PRM-151). ZPN is a recombinant form of human pentraxin-2 (PTX2) that has shown clinical activity as monotherapy and in combination with ruxolitinib (RUX) in a phase II trial in patients with Int-1/-2 or high risk MF (NCT01981850). In stage 2 of this study, patients ineligible for, intolerant of, or with an inadequate response to RUX were randomised to receive 0.3, 3.0, or 10.0 mg/kg ZPN on Days 1, 3, and 5 of Cycle 1, and every 4 weeks thereafter for up to 9 cycles. We demonstrate the potential of quantitative image analysis to augment and refine conventional expert histological assessment of MF.