Researchers identified a number of reasons why patients with myelofibrosis discontinued ruxolitinib and characterized baseline predictors of discontinuation in a study recently published in Cancer.
This multicenter, observational, retrospective study included patients treated at 20 European hematology centers participating in the JUMP trial (ClinicalTrials.gov Identifier: NCT01493414). Clinical and laboratory data for 524 patients who received ruxolitinib for myelofibrosis were recorded in a centralized, electronic, clinical database between 2011 and 2018. The study assessed the influence of reasons for drug discontinuation, disease phase at discontinuation, and salvage therapies on survival outcomes.
For the 524 patients (female, 41%), median age when starting ruxolitinib was 68 years (range, 24-88). At 1 year, 2 years, and 3 years, 22.2%, 32.4%, and 40.8% of patients, respectively, had discontinued ruxolitinib. At median follow-up of 37 months, 51.1% had discontinued the drug; the median drug exposure was 17.5 months (range, 1-81.7).
Baseline predictors of drug discontinuation identified by multivariate analysis were intermediate-2/high-risk category (hazard ratio [HR], 1.74; 95% CI, 1.25-2.45; P =.001), platelet count below 100 x 109/L (HR, 2.27; 95% CI, 1.46-3.55; P <.001), transfusion-dependent anemia (HR, 1.46; 95% CI, 1.02-2.10; P =.04), and unfavorable karyotype (HR, 2.10; 95% CI, 1.24-3.56; P =.01).
For surviving patients (81.3%), the reasons for discontinuation were lack (22.9%) or loss (11.9%) of a spleen response, ruxolitinib-related adverse events (27.5%), progression to blast phase (23.4%), ruxolitinib-unrelated adverse events (9.2%), and allogeneic transplantation during response (5.1%).
Median overall survival (OS) after ruxolitinib was 13.2 months. Patients who discontinued ruxolitinib in chronic phase had significantly longer median OS compared with those who discontinued in the blast phase (27.5 vs 3.2 months; P <.001). Patients who had salvage therapy (investigational agents or ruxolitinib rechallenge) had improved median OS compared with those who received only conventional therapies (40.5 vs 28.9 months; P =.04)
“The survival of patients with myelofibrosis after discontinuation of ruxolitinib is poor, particularly for those who discontinue in blast phase,” the researchers concluded. “Salvage therapies can improve outcome, emphasizing the need for novel therapies.”
1. Palandri F, Breccia M, Bonifacio M, et al. Life after ruxolitinib: Reasons for discontinuation, impact of disease phase, and outcomes in 218 patients with myelofibrosis [published online December 20, 2019]. Cancer. doi:10.1002/cncr.32664