Patient-reported Outcomes and Quality of Life in Anemic and Symptomatic Patients With Myelofibrosis: Results From the MOMENTUM Study.

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm that typically manifests with debilitating symptoms that progressively worsen, negatively impacting patients' quality of life. Fatigue is a multifactorial and burdensome MF-related symptom due to its severity, persistence, and prevalence, with anemia a contributing factor and major unmet need. Clinical trials of the Janus kinase (JAK)1/JAK2/activin A receptor type 1 inhibitor momelotinib have shown consistent anemia benefits, in addition to improvements in MF-related symptoms. The phase 3 MOMENTUM trial in symptomatic and anemic patients met its primary end point, with a greater proportion having a Myelofibrosis Symptom Assessment Form (MFSAF) Total Symptom Score (TSS) reduction ≥50% at week 24 with momelotinib versus danazol. To support the positive primary end point result, we conducted longitudinal, responder, and time-to-event analyses of patient-reported outcomes from MOMENTUM, as measured by the MFSAF, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and Patient-Reported Outcomes Measurement Information System (PROMIS) assessments. These analyses demonstrated rapid and durable response benefits with momelotinib, with achievement of first TSS response by day 29 and continued improvement over time. Improvements favored momelotinib versus danazol for each MFSAF individual item, and greater improvements were observed for disease- and cancer-related fatigue and physical functioning at week 24, with significant results for multiple items/domains across the 3 assessments. These findings are consistent in demonstrating that momelotinib provides substantial symptom benefit.

A Novel RUNX1 Genetic Variant Identified in a Young Male with Severe Osteoporosis.

This case describes a young man with an unusual cause of severe osteoporosis and markedly deranged bone microarchitecture resulting in multiple fractures. A potentially pathogenic germline variant in the runt-related transcription factor 1 (RUNX1) gene was discovered by a focused 51-gene myeloid malignancy panel during investigation for his unexplained normochromic normocytic anemia. Further bone-specific genetic testing and a pedigree analysis were declined by the patient. Recent experimental evidence demonstrates that RUNX1 plays a key role in the regulation of osteogenesis and bone homeostasis during skeletal development, mediated by the bone morphogenic protein and Wnt signaling pathways. Therefore, rarer causes of osteoporosis, including those affecting bone formation, should be considered in young patients with multiple unexpected minimal trauma fractures. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.