Clinical Benefit of Simtuzumab Inconsistent for Myelofibrosis

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Simtuzumab demonstrated encouraging activity in patients with myelofibrosis in early clinical trials.
Simtuzumab demonstrated encouraging activity in patients with myelofibrosis in early clinical trials.

Although well tolerated, simtuzumab monotherapy or with ruxolitinib did not confer clinical benefit or reduce bone marrow fibrosis consistently in patients with myelofibrosis by 24 weeks, a study published in the British Journal of Haematology has shown.1

Simtuzumab is a monoclonal antibody that inhibits extracellular matrix enzyme lysyl oxidase-like-2. Because preclinical and early clinical studies of simtuzumab demonstrated encouraging activity and tolerability in patients with myelofibrosis, researchers sought to evaluate the efficacy and safety of simtuzumab with or without ruxolitinib in patients with myelofibrosis.


For the open-label, phase 2 trial ( Identifier: NCT01369498), investigators enrolled 54 patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis. Participants were randomly assigned to receive simtuzumab alone at a dose of 200 mg or 700 mg or simtuzumab 200 mg or 700 mg plus ruxolitinib for 24 weeks.

Results showed no clinical benefit with simtuzumab alone or in combination with ruxolitinib at 24 weeks. Two patients treated with simtuzumab 700 mg, 2 patients treated with simtuzumab 700 mg plus ruxolitinib, and 1 patient given simtuzumab 200 mg with ruxolitinib achieved reduced bone marrow fibrosis scores at 24 weeks; however, a similar number of patients exhibited increased bone marrow fibrosis.

In addition, simtuzumab therapy did not meaningfully improve hematologic parameters or reduce spleen size or symptoms associated with myeloproliferative neoplasms.

The most common adverse events were those frequently associated with myelofibrosis, including constitutional symptoms such as pyrexia and extremity pain and reductions in hematologic parameters. One patient experienced an infusion reaction.


1. Verstovsek S, Savona MR, Mesa RA, et al. A phase 2 study of simtuzumab in patients with primary, post-polycythaemia vera or post-essential thrombocythaemia myelofibrosis. Br J Haematol. 2017 Feb 21. doi: 10.1111/bjh.14501 [Epub ahead of print]

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