Analysis of Symptom Improvements in Patients With MF Receiving Momelotinib in the SIMPLIFY Studies

A recent study by Ruben A. Mesa, DO, Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, North Carolina, and colleagues investigated changes in total symptom scores (TSS) and individual symptom scores of patients with myelofibrosis who participated in the phase 3 SIMPLIFY-1 and SIMPLIFY-2 studies (Cancer Med. 2023;12(9):10612-10624. doi:10.1002/cam4.5799).

The SIMIPLIFY-1 noninferiority study evaluated 432 intermediate- and high-risk patients with myelofibrosis (MF) who had not previously received Janus kinase inhibitors and were randomly assigned to receive momelotinib or ruxolitinib at a 1:1 ratio. The SIMPLIFY-2 superiority study examined 156 patients with MF who had been treated with ruxolitinib for ≥28 days and were randomly assigned momelotinib or best available therapy (BAT) at a 2:1 ratio; ruxolitinib was the BAT for 88.5% of patients. For both studies, researchers distributed an eight-item questionnaire (Myeloproliferative Neoplasm Symptom Assessment Form [MPN-SAF], version 2) to the patients for the first 24 weeks of the clinical trials to assess symptom burden.

For their study, Dr Mesa and colleagues aimed to support the findings of the two SIMPLIFY studies and determine whether patients experienced symptom improvements while receiving the MF therapies momelotinib, ruxolitinib, or BAT. To do this, the researchers evaluated longitudinal changes in the baseline TSS over a 24-week period and the patients’ individual symptom scores using mixed-effect model repeated measure (MMRM) methodology with individual item–level analyses. The MMRM model was used to evaluate the mean change reported in the MPN-SAF from baseline every 4 weeks up to 24 weeks for each patient visit. Fixed and random covariates included treatment, time, treatment-by-time-interaction, age, race, and baseline MPN-SAF TSS. In addition, the authors used generalized estimating equations to assess the treatment-related differences in the odds of “improved” vs “stable” or “declined/worsened” per responses from the questionnaire.

Overall, Dr Mesa and colleagues found that in SIMPLIFY-1, both the ruxolitinib and momelotinib treatment arms experienced similar symptom improvements, with a TSS difference of <1.5 points between the two groups for each postbaseline visit. Generally, higher rates of symptom improvement were observed in the symptomatic patients in SIMPLIFY-1 compared to the overall population, with low rates of declined/worsened symptoms.

Most of the patients in both studies experienced stability or improvement from baseline to week 24 in the overall and symptomatic patient populations, with stability being defined as a change of at most one point, and improvement being defined as a change of at least two points. However, patients in the SIMPLIFY-2 study (both symptomatic and overall population) who were treated with momelotinib had lower rates of symptoms declining/worsening than the patients who had received BAT.

The researchers acknowledged that there were several limitations in the study stemming from “design nuances” in both the SIMPLIFY-1 and SIMPLIFY-2 trials. These design nuances included baseline severity not being considered part of the criteria for participants in SIMPLIFY-1, which led to a high number of asymptomatic patients in the trial. In addition, SIMPLIFY-2 was an open-label trial, which could be considered more biased than a blinded trial. However, the researchers adjusted for this potential bias by conducting several item- and domain-level analyses, and the impact of the open-label design was negligible.

“This study, together with other evidence from SIMPLIFY-1 and SIMPLIFY-2, demonstrates that momelotinib addresses the key hallmark features of MF and the unmet medical needs for patients with MF,” said the researchers.

According to Dr Mesa and colleagues, the SIMPLIFY studies show that when patients are treated with momelotinib they experience symptom improvements, including reduced transfusions, reduction in spleen size, and decreased anemia. This study’s deeper analysis at the item level further contextualizes the SIMPLIFY studies’ TSS findings regarding the symptomatic benefits of momelotinib for patients with MF.

Sourced from the Journal of Clinical Pathways