Ropeginterferon Alfa 2b Plus Ruxolitinib for Myelofibrosis

Inclusion Criteria: * Willing and able to provide informed consent * Age ≥18 years * Diagnosis of Overt Myelofibrosis (primary, post-ET, or post-PV) per World Health Organization (WHO) 2022 diagnostic criteria * Intermediate-1, Intermediate-2, or high-risk disease by Dynamic International Prognostic Scoring System (DIPSS) * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Platelet count ≥75 x 109/L prior to dosing on Cycle 1 Day 1 * Absolute neutrophil count ≥0.5 x 109/L prior to dosing on Cycle 1 Day 1 * Peripheral blast count ≤10% prior to dosing on Cycle 1 Day 1 * Women of childbearing potential and fertile men must agree to use an approved method of contraception from screening until 30 days after the last dose of ropeginterferon and ruxolitinib. * Patients with suboptimal response to ruxolitinib as per one of the below: i. Relapsed: Ruxolitinib treatment for ≥3 months with spleen regrowth, defined as \<10% SVR or \<30% decrease in spleen size from baseline, following an initial response\* ii. Refractory: Ruxolitinib treatment for ≥3 months with \<10% SVR or \<30% decrease in spleen size from baseline. \* Response to ruxolitinib is defined as a ≥35% reduction in spleen volume from baseline, or a ≥50% reduction in spleen size for baseline spleen sizes \>10 cm below left costal margin (LCM); a non-palpable spleen for baseline spleen sizes between 5-10 cm below LCM; or not eligible for spleen response for baseline spleen \<5 cm below LCM. Exclusion Criteria: Subjects will not be eligible for participation if they meet any of the following exclusion criteria: * Prior or current use of interferon alfa (IFNα) preparations for MPN * Patients currently on other investigational therapy (ies) * Contraindications or hypersensitivity to IFNα preparations * History of organ and haematopoietic stem cell transplantation * History of splenectomy * Pregnant or lactating females, or females planning to become pregnant at any time during the study * Documented autoimmune disease at screening * Infection with human immunodeficiency virus (HIV) * Active and uncontrolled infections with hepatitis B virus (HBV) and hepatitis C virus (HCV). Please note that patients on antiviral therapy with undetectable HBV DNA and HCV RNA may be recruited. * Evidence of severe retinopathy including but not limited to macular degeneration, diabetic retinopathy and hypertensive retinopathy. * History of clinically significant neuropsychiatric conditions including but not limited to depression and epilepsy. * Clinically significant neuropsychiatric conditions including but not limited to depression and epilepsy. * Concurrent second active and non-stable malignancy (patients with a concurrent second active but stable malignancy, i.e., non-melanoma skin cancers, are eligible) * Evidence of alcohol or drug abuse within 6 months * Evidence at the time of Screening of significant renal or hepatic insufficiency (unless due to hemolysis) as defined by any of the following local lab parameters: * Calculated glomerular filtration rate (GFR; using the Cockcroft-Gault equation) \<40 mL/min or serum creatinine \>1.5 x the local upper limit of normal * Aspartate transaminase (AST) or alanine aminotransferase (ALT) ≥2.5 x the local upper limit of normal * Unwilling or unable to comply with the study protocol