MPN disease burden, quality of life, and treatment patterns

The ongoing longitudinal, non-interventional, observational, prospective MOST study is evaluating the disease and demographic characteristics, disease burden, quality of life, and treatment patterns of patients with specific risk categories of myelofibrosis or essential thrombocythaemia. Two separate analyses from this trial were presented.

Myelofibrosis in MOST

Myelofibrosis is an advanced Philadelphia chromosome-negative myeloproliferative neoplasm (MPN) characterised not only by bone marrow fibrosis, but also by extramedullary haematopoiesis, cytopenia, splenomegaly, heavy constitutional symptom burden, and diminished quality of life. Median survival of these patients varies markedly depending on disease risk status. Treatment decisions are thus risk-adapted and may involve a variety of factors, including prognosis and symptomatology. However, real-world data regarding factors that contribute to therapy initiation and choice in patients with lower-risk myelofibrosis is limited.

The first analysis of MOST (NCT02953704) study data assessed disease and demographic characteristics, as well as treatment patterns in low-risk patients with myelofibrosis. Dr Rami S. Komrokji (H. Lee Moffitt Cancer Center and Research Institute, Florida, USA) presented the results [1]. Patients included in the analysis had low-risk myelofibrosis by the Dynamic International Prognostic Scoring System (DIPSS), or intermediate (INT)-1 risk by age >65 years alone. A substantial proportion of both low- and INT-1-risk patients who had received treatment before enrolment were not being treated at the time of enrolment (56.5% and 59.2%, respectively). Mean Total Symptom Score (TSS) was lower in low- versus INT-1-risk patients, but the proportion of patients with TSS ≥20 was greater in treated versus untreated patients in both low- and INT-1 risk groups. So, treated patients had greater patient-reported symptom burden compared with untreated patients. This suggests that high symptom burden may contribute to the decision for treatment in lower-risk myelofibrosis.

Although watch-and-wait is a therapeutic option, the finding that many of these lower-risk patients had received prior therapies suggests an unmet need for effective and tolerable second-line treatment options. Prospective studies are needed to evaluate if symptom burden will change after therapy initiation. Future analyses of MOST will assess the longitudinal evolution of the clinical characteristics and treatment patterns in patients with myelofibrosis.

Essential thrombocythaemia in MOST

Essential thrombocythaemia is a chronic MPN characterised by thrombocytosis and increased risk of thrombotic events and haemorrhage. Treatment of essential thrombocythaemia is risk-adapted, focused on preventing thrombosis and bleeding and minimising symptoms. However, real-world data regarding factors contributing to treatment initiation and therapy choice in this setting are limited.

Dr Michael R. Grunwald (Levine Cancer Institute, North Carolina, USA) presented data of the clinical characteristics of low- and high-risk patients with essential thrombocythaemia enrolled in MOST. Patient-reported symptom burden was assessed using the MPN-Symptom Assessment Form (MPN-SAF). Mean MPN-SAF TSS was significantly higher for low- versus high-risk patients (P=0.0007), as were several individual symptom scores (abdominal discomfort, P=0.0081; concentration, P=0.0014; numbness/tingling, P=0.0361; night sweats, P<0.0001; itching, P=0.0131; bone pain, P=0.0206; weight loss, P=0.0469). Physician-reported signs and symptoms were generally more common in low- versus high-risk patients, with differences between risk groups reaching significance for headache (P=0.0009) and abdominal pain (P=0.0455) [2].

This real-world data indicates that despite treatment, low-risk patients had greater patient-reported symptom burden and physician-reported signs/symptoms than high-risk (treated or untreated) patients. This suggests that current management (most commonly with hydroxyurea in this analysis) may not address symptoms in low-risk patients. Notably, nearly 60% of currently untreated high-risk patients had been previously treated. This highlights an unmet need for effective and tolerable second-line treatments in patients with high-risk essential thrombocythaemia [2]. Further analyses from MOST will help define changes in the clinical and treatment characteristics of patients with essential thrombocythaemia over time.

1. Komrokji RS, et al. To Treat or Not to Treat? Understanding Treatment Patterns in Patients with Lower-Risk Myelofibrosis at the Time of Enrollment in the MOST Study. 62^nd ASH Annual Meeting, 5-8 December 2020. Abstract 152.
2. Grunwald MR, et al. Clinical Characteristics and Treatment Patterns By Risk Stratification in Patients with Essential Thrombocythemia: An Analysis of the MOST Study. 62^nd ASH Annual Meeting, 5-8 December 2020. Abstract 1258.

Posted on 18 February, 20217 April, 2021