While 60% of cases of myelofibrosis occurs in individuals over age 65 and the proportion of patients affected by the disease continues to rise with age, no studies had analyzed how well older patients responded to ruxolitinib, a JAK1/2 inhibitor that can reduce splenomegaly and other symptoms—until now.

All current prognostic models consider older age a significant negative factor in survival, resulting in some older patients being classified as intermediate-1 or intermendiate-2 risk solely based on their age. A recent study in the British Journal of Haematology, however, found that patients over age 75 respond as well to ruxolitinib as those age 65-74 with no greater rates of discontinuation.

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The researchers determined that the presence of high molecular risk mutations had at least as significant effect on survival as age.

The multicenter observational retrospective JUMP trial enrolled 291 patients over age 65 with myelofibrosis who were treated at 23 European hematology centers between June 2011 and July 2017. Participants had an average age of 73.1 years at the start of ruxolitinib therapy.

Among the 253 patients who had evaluable spleen response, 125 (49.4%) achieved spleen response at some point in the three years after starting ruxolitinib, with 25.75 and 35% of evaluable patients achieving response at three and six months, respectively. The researchers saw no significant difference in spleen response overall or at the three and six month evaluations between patients 65-74 (49.7%, 25.5% and 34.8%) and those over age 75 (49%, 26% and 35.2%).

Reduction in systemic symptoms showed a similar pattern. More than 85% of all patients achieved a symptom response (50% or greater reduction in the Myeloproliferative Neoplasm Symptom Assessment Form Derived Total Symptom Score) within three years of treatment initiation. No significant difference emerged between the 65-74 year old group and those over age 75 in terms of system response, overall (85.4% vs 86.1%), at three months (78.0% vs 74.8%) or at six months (85.7% vs 80.7%).

A higher proportion of the oldest patients who did not have transfusion-dependent anemia at baseline developed any anemia during the study at 98.6% compared to 90.2% of the 65-74 year old group. Transfusion-dependent anemia occurred at similar rates in the two groups, 31.7% for the 65-74 year old group and 38.6% for those over 75.

The oldest group experienced more thrombocytopenia, but at grade 3 or 4, the rates were similar between the two age groups. The researchers found that infection was also not significantly affected by older age. After adjustment of the risk of death, the cumulative incidence of ruxolitinib discontinuation was similar between the two groups as well. The same was true for progression to acute leukemia.

Presence of high-molecular risk (HMR) genes including ASXL1, EZH2, IDH1/2 had significant association with worse survival, regardless of patient age. “Indeed, elderly patients with [less than] 2 HMR genes had a comparable survival to older patients with [2 or more] HMR mutated genes,” the authors said. Elderly (over age 75) patients with HMR genes had the worse survival and patients 65-74 without HMR genes had the best survival.

The authors concluded that “a favourable HMR molecular status may overcome the negative impact of older age and that mutations—more than aging—may have a driver/determinant effect on patient survival.”