In the primary analysis of a phase 3 study, ruxolitinib reduced spleen length and symptoms in patients with myelofibrosis, according to results published in British Journal of Haemotology.
In the primary analysis of a phase 3 study, ruxolitinib, a Janus kinase (JAK) 1/JAK2 inhibitor, reduced spleen length and symptoms in patients with myelofibrosis (MF), according to results published in British Journal of Haemotology.
The JAK Inhibitor Ruxolitinib in Myelofibrosis Patients (JUMP) study was a global, single-arm, open-label, phase 3b, expanded-access trial. With 2233 patients, it is the largest and most expansive trial in patients with MF treated with ruxolitinib. In the study results, the authors presented the safety and efficacy results for all patients and a subgroup analysis (n = 138) of patients with low platelet counts (<100 x 109/1) at baseline.
The primary end point of JUMP was safety and tolerability or ruxolitinib by frequency, duration, and severity of adverse events (AEs).
The majority of patients were either intermediate-1 (37.4%) or intermediate-2 (33.8%) risk based on the dynamic International Prognostic Scoring System. The patients with low platelet counts at baseline had “disease characteristics that were consistent with more advanced disease,” based on hemoglobin levels and mean palpable spleen length, the authors noted.
More than half (57.5%) of all patients completed their treatment per protocol and the primary reason for discontinuation was AEs (18.1%), followed by disease progression (9.1%), and death (4.5%). The median exposure to ruxolitinib was 12.4 months; 51% of patients had more than 1 year of exposure and 30% and 13% of patients had greater than 2 and 3 years of exposure, respectively. However, patients in the low-platelet cohort had a lower median exposure (8.3 months).
The most common hematologic AEs were anemia (59.5%) and thrombocytopenia (53.5%). However, these AEs were manageable, since only 2.0% of patients with anemia and 3.4% of patients with thrombocytopenia discontinued treatment due to these AEs. Serious AEs included pneumonia (5.5%), anemia (4.2%), pyrexia (3.5%), cardiac failure (1.9%), dyspnea (1.6%), respiratory failure (1.2%), thrombocytopenia (1.1%), and urinary tract infection (1.0%).
More than half (56.5%) of patients with splenomegaly achieved a 50% or greater reduction from baseline to week 24 in palpable spleen length. By week 48, 61.4% had achieved a response and by week 96, 66.5% had achieved a response. Approximately a quarter (24.7%) of patients had a resolution of splenomegaly.
Overall survival probability was estimated at 94% (95% CI, 92%-95%) at 48 weeks and 87% (95% CI, 85%-89%) at 96 weeks. In addition, there were 205 deaths (9.2%) either on treatment or reported up to 28 days after the end of treatment.
The authors concluded that the findings from JUMP confirm the findings from the phase 3 COMFORT studies, while providing additional efficacy and safety evidence. They also noted that continued analysis is needed to determine the long-term efficacy of ruxolitinib.
“However, it is important to interpret our findings with caution given the limitations associated with a single-arm study and the small number of patients in the [intermediate-1]–risk and low-platelet cohorts; additionally, because comparisons of patient subgroups were conducted as a post-hoc analysis, no statistical testing was performed,” they explained.
Al-Ali HK, Greisshammer M, Foltz L, et al. Primary analysis of JUMP, a phase 3b, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis, including those with low platelet counts. Br J Haematol. 2020;189(5):888-903. doi:10.1111/bjh.16462