Patient-reported Outcomes and Quality of Life in Anemic and Symptomatic Patients With Myelofibrosis: Results From the MOMENTUM Study

Abstract

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm that typically manifests with debilitating symptoms that progressively worsen, negatively impacting patients' quality of life. Fatigue is a multifactorial and burdensome MF-related symptom due to its severity, persistence, and prevalence, with anemia a contributing factor and major unmet need. Clinical trials of the Janus kinase (JAK)1/JAK2/activin A receptor type 1 inhibitor momelotinib have shown consistent anemia benefits, in addition to improvements in MF-related symptoms. The phase 3 MOMENTUM trial in symptomatic and anemic patients met its primary end point, with a greater proportion having a Myelofibrosis Symptom Assessment Form (MFSAF) Total Symptom Score (TSS) reduction ≥50% at week 24 with momelotinib versus danazol. To support the positive primary end point result, we conducted longitudinal, responder, and time-to-event analyses of patient-reported outcomes from MOMENTUM, as measured by the MFSAF, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and Patient-Reported Outcomes Measurement Information System (PROMIS) assessments. These analyses demonstrated rapid and durable response benefits with momelotinib, with achievement of first TSS response by day 29 and continued improvement over time. Improvements favored momelotinib versus danazol for each MFSAF individual item, and greater improvements were observed for disease- and cancer-related fatigue and physical functioning at week 24, with significant results for multiple items/domains across the 3 assessments. These findings are consistent in demonstrating that momelotinib provides substantial symptom benefit.

Graphical abstract

Figure 1.

MFSAF individual item scores and descriptive responder analysis by corresponding MCTs. (A) MFSAF individual item scores at baseline and week 24 in the momelotinib and danazol arms. (B) Descriptive responder analysis for MFSAF at week 24; response was defined as a reduction from baseline ≥ MCT (≥3-point score reduction). Response rate difference and P values were stratified by Cochran-Mantel-Haenszel with missing week 24 results as nonresponders. ^aP < 0.05. MCT = meaningful change threshold; MFSAF = Myelofibrosis Symptom Assessment Form.

Figure 2.

Time to first MFSAF total symptom score percent change response in randomized treatment period. ^aHazard ratio (momelotinib divided by danazol) is from stratified Cox proportional hazards model with a single factor of treatment group, stratified by baseline MFSAF TSS (≥22 vs <22), baseline palpable spleen length below the LCM (≥12 vs <12 cm), and baseline RBC or whole blood units transfused in the 8-wk period before randomization (0, 1–4, and ≥5). ^bP value is from log-rank test stratified by baseline MFSAF TSS (≥22 vs <22), baseline palpable spleen length below the LCM (≥12 vs <12 cm), and baseline RBC or whole blood units transfused in the 8-wk period before randomization (0, 1–4, and ≥5). LCM = left costal margin; MFSAF = Myelofibrosis Symptom Assessment Form; RBC = red blood cell; TSS = Total Symptom Score.

Figure 3.

Time to first MFSAF fatigue response in randomized treatment period. ^aHazard ratio (momelotinib divided by danazol) is from stratified Cox proportional hazards model with a single factor of treatment group, stratified by baseline MFSAF TSS (≥22 vs <22), baseline palpable spleen length below the LCM (≥12 vs <12 cm), and baseline RBC or whole blood units transfused in the 8-wk period before randomization (0, 1–4, and ≥5). ^bP value is from log-rank test stratified by baseline MFSAF TSS (≥22 vs <22), baseline palpable spleen length below the LCM (≥12 vs <12 cm), and baseline RBC or whole blood units transfused in the 8-wk period before randomization (0, 1–4, and ≥5). LCM = left costal margin; MFSAF = Myelofibrosis Symptom Assessment Form; RBC = red blood cell; TSS = Total Symptom Score.

Figure 4.

Descriptive responder analysis for EORTC QLQ-C30 at week 24 by corresponding MCTs. Response rate difference and P values were stratified by Cochran-Mantel-Haenszel with missing week 24 results as nonresponders. ^aP < 0.05; ^bResponse was defined as a reduction from baseline ≥MCT; MCT defined as >(1) 7-, (2) 8-, (3) 9-, (4) 10-, (5) 11-, (6) 12-, and (7) 13-point improvement from baseline. EORTC QLQ-C30 = European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; HRQOL = health-related quality of life; MCT = meaningful change threshold.

Figure 5.

Descriptive responder analysis for PROMIS at week 24 by corresponding MCTs. Response rate and P values were stratified by Cochran-Mantel-Haenszel with missing week 24 results as nonresponders. ^aP < 0.05; ^bResponse was defined as a reduction from baseline ≥MCT; MCT defined as >(1) 6-point score reduction from baseline. ≥MCT; MCT defined as >(1) 6-point score reduction from baseline. MCT = meaningful change threshold; PROMIS = Patient-Reported Outcomes Measure Information System.

Figure 6.

Time to first PROMIS physical function short form 10b response. ^aHazard ratio (momelotinib divided by danazol) is from stratified Cox proportional hazards model with a single factor of treatment group, stratified by baseline MFSAF TSS (≥22 vs <22), baseline palpable spleen length below the LCM (≥12 vs <12 cm), and baseline RBC or whole blood units transfused in the 8-wk period before randomization (0, 1–4, and ≥5). ^bP value is from log-rank test stratified by baseline MFSAF TSS (≥22 vs <22), baseline palpable spleen length below the LCM (≥12 vs <12 cm), and baseline RBC or whole blood units transfused in the 8-wk period before randomization (0, 1–4, and ≥5). LCM = left costal margin; MFSAF = Myelofibrosis Symptom Assessment Form; NC = not calculable; PROMIS = Patient-Reported Outcomes Measure Information System; RBC = red blood cell; TSS = Total Symptom Score.