Burden of Disease and Clinical Responses in Low and Intermediate-1 Risk Myelofibrosis Patients Treated with Ruxolitinib

Myelofibrosis (MF) is a hematologic neoplasm characterized by variable degrees of cytopenias/ myeloproliferation, extramedullary hematopoiesis, disease-related constitutional symptoms and an increased risk for acute myeloid leukemia (AML) transformation. Ruxolitinib, a JAK1/2 inhibitor is FDA approved for the management of intermediate to high-risk MF. However, intermediate-2 and high-risk MF patients accounted for 99% of patients (pts) in the 2 pivotal trials that led to the approval of ruxolitinib in North America, Australia and Europe (COMFORT 1 and COMFORT 2 studies). However, even low and intermediate-1 (int-1) risk MF pts could have a high burden of disease. Here we report our experience of using ruxolitinib in MF pts stratified as low and int-1 risk by the Dynamic International Prognostic Scoring System (DIPSS). A total of 25 pts with low and Int-1 risk disease were treated with ruxolitinib at the Cleveland Clinic and Northwestern University. The median age of the cohort was 61 yrs (range=33-87; males=9, females=16). The median total symptom score (TSS) by Myeloproliferative Neoplasm Symptom Assessment Form (MPN SAF) was 20. The median pre-treatment spleen size by palpation was 13 cm below the left costal margin. Baseline median bone marrow (BM) fibrosis grading was 2 (on a scale 0-3; grade 1 N=3, grade 2 N=11, and grade 3 N=11). The indications for starting ruxolitinib were constitutional symptoms (fatigue N=20, night sweats N=4, pruritus N=1) and splenomegaly (N=13). The median starting dose was 5 mg twice daily, 10mg twice daily at 3 months and 6 months, and 5mg twice daily at 12 months. The median dose at last follow up was 10 mg twice daily. The median duration of treatment was 12 months. There was a median 73% reduction in the MPN SAF TSS compared to baseline (P 0.05) further supporting the high burden of disease observed even in low and int-1 risk MF patients. In conclusion, pts with low/int-1 risk MF have a high burden of disease and can achieve meaningful clinical responses to ruxolitinib similar to int-2/ high risk MF pts without severe toxicity. Larger studies are needed to further evaluate the safety and efficacy of ruxoltinib in this patient population. Disclosures No relevant conflicts of interest to declare.