Citation: British Journal of Haematology. 2019, 185, 8-9
Author: Mead A.; Butt N.; Nagi W.; Whiteway A.; Kirkpatrick S.; Rinaldi C.; Roughley C.; Ackroyd S.; Ewing J.; Neelakantan P.; Garg M.; Harrison C.; Tucker D.; Collington S.; Chiu G.; Hickey J.; Somervaille T.
Abstract: Current treatment options for myelofibrosis (MF) are diverse; typically active treatments manage MF-related symptoms and are not disease modifying. Patients who are initially asymptomatic and those at low risk for progression are often observed without active treatment ('watch and wait') until the appearance of symptoms or progression. There are limited real-world data on the management of patients with MF in the United Kingdom (UK). The REALISM UK study aims to document the early management pathways for patients with MF in routine clinical practice. REALISM UK is a multi-centre, retrospective, non-interventional study ongoing in 15 UK secondary care centres. Eligible patients were those aged >= 18 years at diagnosis of MF, with diagnosis > 6 months and <= 5 years prior to data collection and with >= 1 follow-up visits. Data on patient demographics, clinical characteristics MF management strategies and outcomes were collected from patients' medical records; the observation period was from the date of MF diagnosis until data collection. The primary endpoint was the time from diagnosis to active treatment. Herein we report results from an interim analysis. A total of 200 patients were recruited (64% [127/200] with primary MF (PMF), 36% [73/200] with secondary [2degree] MF). The median age at MF diagnosis was 69.7 (Interquartile range [IQR] 63.5-75.7) years and 63% (125/200) had a JAK2 mutation. 60% (119/200) of patients had International Prognostic Scoring System (IPSS) categories of intermediate-2 (int-2) or high at diagnosis. Common documented features of disease at diagnosis included an enlarged spleen (47%, 94/200), anaemia (44%, 88/200), and constitutional symptoms (e.g. night sweats, unexplained fever or weight loss, [30%, 60/200]). The median time from diagnosis to active treatment was 0.0 (IQR 0.0-369.3) days (n = 200). During the study observation period 'watch and wait' was the first management strategy for 47% (94/200) of patients (PMF, 56% [71/127]; 2degreeMF, 32% [23/73]), with 69% (65/ 94) progressing to active treatment. In these 94 patients (including 29 with no active treatment at data collection), the median (IQR) time from diagnosis to active treatment (or data collection) was 409.0 (141.5-650.0) days (IPSS low: 280.5 [195.0-369.3] days [n = 4]; IPSS int-1: 284.5 [98.0-625.3] days [n = 24]; IPSS int-2 461.0 [259.5-737.3] days [n = 30]; IPSS high: 119.0 [60.3-277.0] days [n = 12]). Active treatment was started at diagnosis for 53% (106/200) of patients. A total of 409 management strategies (defined as any clinical decision on patient management) were observed. The commonest strategies were 'watch and wait' (26% [107/409]), ruxolitinib (25% [102/409]), hydroxycarbamide (17% [68/409]) and allogenic stem cell transplantation (3% [11/409]). The median treatment duration (during the observation period) was 378 (IQR 162.3-690.8) days for ruxolitinib and 336.5 (IQR 108.5-767.5) days for hydroxycarbamide. 47 (24%) patients died between diagnosis and data collection. The recorded causes of death were: MF-related (including progression 38% [18/47]), other malignancies (9% [4/47]), infection (9% [4/47]) and heart failure (6% [3/47]); cause unknown in 38% (18/ 47) cases. The results of this interim analysis suggest there are a broad range of management strategies for patients with MF, reflecting the symptomatic treatment of MF. Many of the patients were observed without active treatment following diagnosis, and the most common cause of death was MF-related.
