Ellen Ritchiea , Anas Al-Janadib, Craig Kessler, Robyn Scherberd, Tricia Kalafutd, Haobo Rend and Ruben Mesa
Introduction
Myelofibrosis (MF) and essential thrombocythemia (ET) are acquired Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), a rare group of malignant blood disorders characterized by abnormal clonal proliferation of at least one myeloid cell line
[1,2]. Hallmark characteristics of MF include splenomegaly, burdensome constitutional symptoms, cytopenia, and progressive bone marrow fibrosis [3,4]. ET is associated with increased platelet and megakaryocyte production, and increased risk of vascular events such as thrombosis and bleeding [1,3].
Patients with MF or ET report a range of symptoms such as abdominal discomfort, bone pain, fatigue, itching, night sweats, unexplained weight loss, and/or fever [5–9]. Additional symptoms common to MF are often related to spleen enlargement and include abdominal pain, left subcostal pain, and early satiety; additional ET symptoms are commonly vasomotor in nature and include headaches, dizziness, erythromelalgia, and concentration problems [1]. The MPN Landmark study demonstrated that these diseaserelated symptoms result in a reduced quality of life (QoL) in a majority of patients with MF and ET (81% and 57%, respectively) [7]. Notably, symptoms adversely affect patients’ QoL in not only those with the most severe disease, but also in those with low prognostic scores and in those in the lowest symptom
severity quartile [7].
Lower-risk patients with MF or ET have previously been reported to have a lower incidence of symptoms [10]; however, the severity and impact of MPN-associated symptoms is not well-recognized in lower-risk patients. Although treatments for both MF and ET are risk-adapted, and are directed at managing the disease and minimizing or improving symptoms [11,12], symptom burden is not included as a risk stratification factor for either MF or ET [12–15]. A practice of observation and monitoring of signs/symptoms for disease progression is recommended for lower-risk asymptomatic MF or low-risk ET [16,17]; however, patients with lower-risk symptomatic MF may receive cytoreductive therapy, ruxolitinib, or interferon at the physician’s discretion [17]. Therefore, characterizing symptom burden in these patients may help guide more effective disease management and treatment strategies.
Patient-reported outcome (PRO) instruments are validated questionnaires often used in observational studies and clinical trials to assess the effect of a treatment or condition from the patient’s perspective [18]. PRO instruments provide important and otherwise clinically difficult to obtain measures of the patient’s perception of their physical, social, and psychological wellbeing [19]. Although most PRO-based assessments
of patients with MF have focused on those with intermediate (INT) or higher risk disease, limited PRO data from patients with lower risk MF have been published. For example, the MPN Landmark study recruited patients with MPNs irrespective of risk category or treatment; of note, most recruited patients with MF had INT-2- or high-risk disease [7]. Therefore, although evidence exists for the effects of symptom burden on QoL in patients with INT-2 and high-risk MF, there are limited data describing the effects of symptom burden on QoL in patients with lower-risk MF. Similarly, little is known about the comparison of PROs in patients with high- versus low-risk ET, and the extent to which ET-directed treatment received relieves symptom burden in these patients. Despite the importance of assessing PROs, a review of a registry of clinical trials (initiated between 2006 and 2016) in patients with MPNs reported that only 19/35 reported on at least one PRO assessment as a study endpoint; of the 19 trials, only nine published a detailed analysis of PRO data [20]. Thus, there is an unmet need for further investigation into the extent to which symptom burden affects the daily lives and QoL of patients with lower risk MF and ET.
The Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST; NCT02953704) is an ongoing noninterventional study designed to collect clinical characteristics, PROs, and treatment patterns of patients with specific risk categories of clinically diagnosed MF and ET in community and academic centers throughout the United States. This analysis assessed patient-reported symptom burden and its effect on QoL, work productivity, and activity in patients with MF and ET at the time of enrollment in MOST.