Evaluating Clinically Meaningful Symptom Benefits and Symptom Change Threshold Among Patients With Myelofibrosis Treated With Momelotinib

Results from the Phase 3 SIMPLIFY-1 and SIMPLIFY-2 Trials

Momelotinib, a Janus kinase (JAK) inhibitor, displayed clinically meaningful symptom benefits among patients with myelofibrosis (MF), according to a study that offers important insight into the appropriateness of the symptom change threshold used in the phase 3 SIMPLIFY-1 and SIMPLIFY-2 trials, as well as further evaluates the percent and absolute thresholds of change considered meaningful in patients with MF. 

To the study authors’ knowledge, this is the first report to publish a significant change threshold in the symptomatic population of intermediate- or high-risk patients with myelofibrosis using anchor-based methods. 

Historical trials, such as the phase 3 SIMPLIFY-1 and SIMPLIFY-2 trials, have established that a symptom response constitutes a reduction of ≥ 50% in total symptoms score at week 24 compared with baseline. However, no prior reports have established whether a 50% symptom response yields a meaningful benefit. 

In this trial, the study authors aimed to establish the meaningful change threshold for these 2 historical trials. Using anchor-based methods applied to the modified Myeloproliferative Neoplasm Symptom Assessment Form v2.0 and Patient Global Impression of Change, the absolute and percentage meaningful change thresholds were measured. They were then used retrospectively to calculate responder rates. To find the treatment-related difference in the probability of improvement, the study authors utilized generalized estimating equations. 

Study results indicated that the meaningful change threshold was 8 points among the JAK inhibitor-naive patient population of the SIMPLIFY-1 trial. In the SIMPLY-2 trial, the meaningful change threshold was 6 points among the group of patients who had been previously treated with JAK inhibitor(s). In both studies, a 32% meaningful change threshold was established, which demonstrated that the historic 50% reduction threshold may be an appropriate choice.

In SIMPLIFY-1, the proportion of patients who achieved a response within 24 weeks of momelotinib versus ruxolitinib based on the absolute meaningful change threshold was comparable, at 39% versus 41%, respectively. In contrast, more patients who were treated with momelotinib achieved a response compared with the best available therapy in the SIMPLIFY-2 trial regarding absolute and percent change meaningful change thresholds. 

Based on these findings, Stacie Hudgens, MA, Clinical Outcomes Solutions, Tucson, Arizona, and study authors concluded that, “Momelotinib provided clinically meaningful symptom benefit for patients with myelofibrosis and provides insight into the appropriateness of the symptom change threshold used in historical studies.”

Source: 

Hudgens S, Verstovsek S, Floden L, et al. Meaningful symptomatic change in patients with myelofibrosis from the SIMPLIFY trials. Value in Health. Published online: February 2, 2024. doi: 10.1016/j.jval.2024.01.014