Applying COMFORT Trial Data: Spleen Response and Survival Benefit Interpretation in Intermediate-1 Risk Patients
Panelists discuss how JAK inhibitor therapy can benefit patients with intermediate-1–risk myelofibrosis despite being studied primarily in higher-risk patients in the COMFORT and JUMP trials.
This segment explores the use of JAK inhibitors in intermediate-1–risk myelofibrosis patients. Dr Vachhani notes that while the COMFORT trials, which led to ruxolitinib approval, enrolled intermediate-2– and high-risk patients, they’re discussing a case with intermediate-1 risk. He asks Dr Rampal about using JAK inhibitors in this lower-risk category.
Dr. Rampal addresses the disconnect between risk stratification tools and clinical practice, pointing out that splenomegaly—a primary end point in COMFORT trials and a major treatment consideration—isn’t included in risk stratification scores. He believes it’s reasonable to extrapolate the benefits seen in COMFORT studies to intermediate-1–risk patients. Additionally, the JUMP study examined ruxolitinib in lower-risk disease and found similar benefits with potentially better tolerability when started earlier.
Dr. Vachhani references the 2024 RUX-MF study from Europe, which enrolled 595 patients with intermediate-1–risk myelofibrosis and found many were very symptomatic despite their lower risk classification. This study demonstrated that intermediate-1–risk patients benefited significantly from ruxolitinib, highlighting the disconnect between risk stratification and symptom burden. The experts agree that JAK inhibitor therapy can be appropriate for symptomatic patients regardless of their formal risk category.
