Momelotinib Is Effective in Treatment for VEXAS Syndrome: Two Cases Within the AGMT Austrian Myeloid Registry

Abstract

VEXAS syndrome is caused by somatic mutations in the UBA1 gene and includes features of both autoinflammatory and myeloid diseases. Among several treatment options, JAK inhibitors have proven effective, especially ruxolitinib. However, anemia is often present in VEXAS syndrome. The novel JAK inhibitor momelotinib is approved for myelofibrosis with anemia. Here, we report of two patients within the Austrian Myeloid Registry of the Austrian Group Medical Tumor Therapy (AGMT), with newly diagnosed VEXAS syndrome and anemia, who were treated with momelotinib. Both patients experienced an improvement in anemia, a decrease in inflammation, and the treatment was well tolerated. VEXAS syndrome (acronym for: vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an autoinflammatory disease caused by somatic mutations in the ubiquitin-like modifier activating enzyme 1 (UBA1) gene. Key clinical features comprise hematological as well as rheumatological, features. Associated hematological conditions include cytopenia, bone marrow failure, myelodysplastic syndrome, increased risk for thromboembolic events, and prominent vacuolization of myeloid and erythroid precursor cells in the bone marrow.

Keywords: JAK inhibitor; VEXAS syndrome; autoinflammation; myelodysplastic syndrome.

Graph 1

Bone marrow cytology with typical features of VEXAS syndrome, including vacuolization of the erythroid and myeloid precursors.

Graph 2

Changes in hemoglobin and CRP levels before and during treatment with momelotinib.