simtuzumab + ruxolitinib

Simtuzumab + ruxolitinib is a **combination therapy** evaluated for patients with myelofibrosis (MF), including primary, post-polycythemia vera MF, and post-essential thrombocythemia MF. **Simtuzumab** is a monoclonal antibody inhibitor of the extracellular matrix enzyme **lysyl oxidase-like-2 (LOXL2)**, thought to reduce fibrosis by inhibiting cross-linking of collagen and elastin in the bone marrow. **Ruxolitinib** is a small molecule **Janus kinase (JAK) 1/2 inhibitor** that reduces spleen size and ameliorates symptoms by blocking dysregulated JAK-STAT signaling. The rationale for their combination was to address both the fibrotic and proliferative aspects of MF, but in clinical studies the combination showed no added clinical benefit over single-agent ruxolitinib, with limited impact on bone marrow fibrosis and hematologic parameters.