The JAK1/2 inhibitor ruxolitinib induced durable improvements in patients with primary and secondary myelofibrosis in the phase III JUMP study. A recent analysis of these findings looked at safety and efficacy of ruxolitinib in disease risk groups, finding that the drug was effective across all risk categories. The results were published in Hematological Oncology.
In this analysis, researchers stratified JUMP participants study included adults with primary or secondary myelofibrosis according to Dynamic International Prognostic Scoring System (DIPSS) risk categories. Information to assess DIPSS status was available for 1,844 of the 2,233 enrolled patients. DIPSS categories were as follows:
- low: 60 patients
- intermediate-1 (int-1): 835 patients
- intermediate-2 (int-2): 755 patients
- high: 194 patients
Ruxolitinib was generally well tolerated across all risk groups, the authors observed, with an adverse event (AE) profile consistent with previous reports. The most common hematologic AEs were thrombocytopenia and anemia, and high-risk patients had the highest rates of grade ?3 AEs.
Overall, 73% of patients experienced ?50% reduction in palpable spleen length at any point during the treatment period. The researchers found that patients in lower-risk categories had the highest rates of response: low, 82.1%; int-1, 79.3%; int-2, 67.1%; high risk, 61.6%.
The median time to spleen length reduction was 5.1 weeks and, again, patients with lower-risk disease had better outcome, with a shorter time to spleen length reduction. Across different measures of symptom improvement, rates of response ranged from 40% to 57%. These improvements were evident beginning at four weeks after ruxolitinib initiation and were maintained throughout the study.
Rates of overall survival (OS) were 92% at 72 weeks after ruxolitinib initiation and 75% at 4.6 years. While median OS was not evaluable for comparison in low-risk and int-1-risk patients, median OS was longer in those with int-2-risk disease than high-risk patients (253.6 vs. 147.3 weeks). By 4.6 years, progression-free and leukemia-free survival rates were higher in lower-risk patients, as well.
The authors concluded that clinical benefit was seen across risk groups, “with more rapid improvements in lower-risk patients, [and] overall, this analysis indicates that ruxolitinib benefits lower-risk DIPSS patients in addition to higher risk.”