A phase 3 study comparing danazol vs momelotinib for the treatment of myelofibrosis (MF) found that momelotinib demonstrated greater improvements in disease-related symptoms, physical function, and health-related quality of life among patients with MF.

These findings were presented at the 64^th ASH Annual Meeting in New Orleans, LA.

MF is associated with disease-related inflammation, anemia, and splenomegaly (an enlarged spleen), often resulting in a hindered health-related quality of life for the patient. “There are no approved treatments for patients with intermediate- and high-risk MF that specifically target anemia, and approved MF therapies for splenomegaly and symptoms often exacerbate anemia,” wrote Ruben Mesa, MD, FACP, UT Health San Antonio MD Anderson Cancer Center, San Antonio, TX, and colleagues. Momelotinib, a Janus kinase (JAK) 1, JAK2, and activin A receptor type 1 inhibitor, has shown symptom, spleen, and anemia benefits among patients with MF. These associated benefits led Dr Mesa and colleagues to conduct a patient-reported health status and health-related quality of life analysis among patients with MF treated with momelotinib vs danazol.

The authors performed patient-reported outcome (PRO) analyses for various assessments among the intent-to-treat (ITT) population, including the Myelofibrosis Symptom Assessment Form (MFSAF) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and they summarized the PRO response analyses by corresponding meaningful change threshold for each PRO. The mixed model for repeated measures was used to analyze longitudinal change from baseline scores, and the treatment effect of momelotinib vs danazol was defined as the odds ratio (OR) for response, 95% confidence interval, and P value. In addition, the researchers utilized the Kaplan-Meier method for the time to first response analysis, a stratified log-rank test to compare treatment arms, and a stratified Cox regression model to estimate hazard ratios (HRs).

Findings from the assessments showed improvements in MF-related symptoms, physical function, and global quality of life associated with momelotinib compared to danazol. The greatest improvements at the 24-week mark were observed in the MFSAF, followed by the Patient-Reported Outcomes Measurement Information System, and the EORTC QLQ-C30.

Results from the MFSAF individual item scores from baseline and week 24 indicated greater improvement in the momelotinib group than in the danazol group based on median scores and mixed model for repeated measures analysis. Night sweats, abdominal discomfort, bone pain, and rib pain, were less severe in the momelotinib group compared to the danazol group. Patients in the momelotinib group had a higher likelihood of response, according to results from the MFSAFtotal symptom score (TSS) response analysis for the form (overall OR of 2.50 throughout the 24-week treatment period). In addition, the time to first response analysis for TSS and individual items showed that HRs ranged from 1.47-3.82, indicating a faster symptom response for more patients in the momelotinib group for TSS.

Responder analyses based on the MFSAF showed that the proportion improved for fatigue was 18.5% in the momelotinib group vs 9.2% in the danazol group. For the EORTC QLQ-C30, responder analyses showed 41.5% improved for fatigue in the momelotinib group vs 21.5% in the danazol group. In both analyses, the authors considered missing data to be a nonresponse.

Physical function in the momelotinib group was 17.7% vs 4.6% in the danazol group, according to the responder analysis using the Patient-Reported Outcomes Measurement Information System assessments. “This trend was supported by shorter times to first response for physical function in more patients in the MMB [momelotinib] group vs the DAN [danazol] group (HR = 1.93, 95% CI 0.95, 3.91),” wrote the Dr Mesa and colleagues.

Results from the EORTC QLQ-C30 regarding the improvement in global quality of life showed a proportion difference of 14.6% between the momelotinib group and the danazol group, favoring momelotinib.

“Consistent with the positive primary endpoint (TSS50) result of the MOMENTUM study, these responder, longitudinal, and time-to-event analyses demonstrate that MMB [momelotinib] provides comprehensive improvements in disease-related symptoms with associated improvement in physical function and overall HRQoL [health-related quality of life] compared with DAN [danazol] in patients with MF,” concluded the authors. 

Reference

Mesa R, Harrison C, Palmer J, et al. The Impact of Momelotinib on Patient Reported Quality of Life for Symptomatic and Anemic Patients with Myelofibrosis: Results from the Phase 3 Momentum Study. Presented at 64th ASH Annual Meeting and Exposition. December 10-13, 2022. New Orleans, Louisiana. Abstract: 4351.