A study presented as part of the ASH 2020 Annual Meeting found that imetelstat improved overall survival (OS) in patients with myelofibrosis (MF) who have relapsed or become refractory to Janus kinase (JAK) inhibitors.
Currently, there are no approved treatment options for patients with MF who are relapsed/refractory to JAK inhibitors.
The two-dose, randomized, single-blinded, phase II IMbark study included 107 patients with relapsed/refractory intermediate-2/high-risk MF. Patients received imetelstat 9.4 mg/kg (n=59) or 4.7 mg/kg (n=48) intravenously every three weeks.
As of February 19, 2020, after a median follow-up of 41.7 months, median OS was 28.1 months in the 9.4 mg/kg group (95% confidence interval [CI], 22.8-31.6) and 19.9 months in the 4.7 mg/kg cohort (95% CI, 17.1-33.9). After accounting for confounding factors of subsequent therapies, including hematopoietic cell transplantation and dose escalation from 4.7 mg/kg to 9.4 mg/kg, similar results were observed.
Patients who achieved symptom response at week 24 had a trend toward longer OS compared with those who did not achieve symptom response or who had no assessment (hazard ratio [HR], 0.79; 95% CI, 0.41-1.51). A similar trend was seen for patients who achieved spleen response at week 24 (HR, 0.46; 95% CI, 0.11-1.92).
In addition, ?20% spleen volume reduction (SVR) was associated with a trend toward better OS compared with ?20% reduction (HR, 0.44; 95% CI, 0.19-1.04). The trend remained with a ?10% SVR cutoff (HR, 0.69; 95% CI, 0.38-1.27).
Among 57 patients with available bone marrow (BM) data, 19 (33%) had ?1 degree of BM fibrosis improvement during the study and had significant longer OS than those who had worsening BM fibrosis (HR, 0.36; 95% CI, 0.13-0.96; P=0.04). A similar trend was observed in 30 patients (53%) with stable versus worsening fibrosis (HR, 0.47; 95% CI, 0.19-1.20).
Increased risk of death was associated with pre-treatment Dynamic International Prognostic Scoring System high risk, Eastern Cooperative Oncology Group performance status, transfusion dependency, higher baseline neutrophils, and lower baseline hemoglobin and platelet values.