Myelofibrosis Survival After Discontinuing Ruxolitinib Differs Based on Reason for Discontinuation

Ruxolitinib is the only targeted therapy available for the treatment of myelofibrosis (MF)-related splenomegaly and symptoms, and while 50% of patients with MF achieve significant clinical responses with ruxolitinib, half the responders stop responding over time.

Following failure with ruxolitinib, there are limited treatment options available and among these patients who fail on the treatment, prognosis is unfavorable, particularly among those who started ruxolitinib with advanced stage disease, according to a study presented at the 60th American Society of Hematology Annual Meeting & Exposition.

The study further indicated that discontinuation because of disease evolution into acute leukemia or because of occurrence of a second solid neoplasia significantly reduced life expectancy.

The researchers assessed retrospective data from a clinical database created in 23 European hematology centers that included 537 patients treated with ruxolitinib from January 2011 to July 2018. Updated information on 442 patients available at the date of July 15 was included.

Spleen and symptom response to treatment were evaluated, and ruxolitinib-related toxicity and infections were graded. Overall survival was estimated from the date of ruxolitinib discontinuation to the date of death or last contact.

After a median follow-up of 30.5 months, 214 of the 442 (48.4%) evaluable patients discontinued ruxolitinib. Among these patients, 43 (20.1%) died while on therapy because of MF progression (34.9%), infection (25.6%), heart disease (16.3%), second neoplasia (7%), hemorrhages (7%), and other causes (9.2%).

Among the remaining 171 patients who discontinued ruxolitinib, median follow-up was 11.3 months. Reasons for discontinuation included drug-related toxicity (28.6%), loss/lack of response (23.4%), MF progression (12.3%), acute leukemia (13.4%), allogeneic stem cell transplantation (ASCT) (11.1%), second solid neoplasia (4.1%), and other unrelated causes (7.1%).

After discontinuing ruxolitinib, 68 patients received 1 line of therapy, 21 received 2 lines, and 9 received more than 2 treatments. Meanwhile, 73 patients did not receive any therapy. Treatments received after ruxolitinib discontinuation, alone or in combination, included hydroxyurea, ASCT, second generation JAK2 inhibitors, splenectomy, azacytidine/decitabine, chemotherapy, investigational agents, danazole, and erythropoietin-stimulating agents.

There were 95 patients who died following ruxolitinib discontinuation due to MF progression (30.5%), acute leukemia (25.4%), infections (14.7%), second neoplasia (9.5%), hemorrhages (4.2%), heart disease (4.2%), ASCT (4.2%), thrombosis (2.1%), and other causes (5.2%). Median survival time following ruxolitinib among the 171 patients was 22.6 months.

Survival following discontinuation was significantly influenced by the dynamic international prognostic score category, transfusion dependency, and driver mutation status at baseline.

While receiving therapy, 45 out of 153 (29.4%) and 123 out of 161 (76.4%) evaluable patients achieved a spleen and symptoms response at any point, but survival was not affected by the previous response to treatment. However, survival significantly varied based on the reason for stopping treatment, with those discontinuing because of acute leukemia evolution/second solid neoplasia having the worst outcome.

Among patients who discontinued treatment in chronic phase, the use of second-generation tyrosine kinase inhibitors and other investigational agents prolonged survival compared with administration of conventional treatments.

Reference

Palandri F, Elli E, Polverelli N, et al. Outcome of patients wth myelofibrosis after ruxolitinib failure: role of disease status and treatment strategies in 214 patients. In: Proceedings from the American Society of Hematology; December 1-4, 2018; San Diego, CA. Abstract 4277.