Real-world tyrosine kinase inhibitor treatment pathways, monitoring patterns and responses in patients with chronic myeloid leukaemia in the United Kingdom: the UK TARGET CML study.

Management of chronic myeloid leukaemia (CML) has recently undergone dramatic changes, prompting the European LeukemiaNet (ELN) to issue recommendations in 2013; however, it remains unclear whether real-world CML management is consistent with these goals. We report results of UK TARGET CML, a retrospective observational study of 257 patients with chronic-phase CML who had been prescribed a first-line TKI between 2013 and 2017, most of whom received first-line imatinib (n = 203). Although 44% of patients required ≥1 change of TKI, these real-world data revealed that molecular assessments were frequently missed, 23% of patients with ELN-defined treatment failure did not switch TKI, and kinase domain mutation analysis was performed in only 49% of patients who switched TKI for resistance. Major molecular response (MMR; BCR-ABL1IS ≤0·1%) and deep molecular response (DMR; BCR-ABL1IS ≤0·01%) were observed in 50% and 29%, respectively, of patients treated with first-line imatinib, and 63% and 54%, respectively, receiving a second-generation TKI first line. MMR and DMR were also observed in 77% and 44% of evaluable patients with ≥13 months follow-up, receiving a second-generation TKI second line. We found little evidence that cardiovascular risk factors were considered during TKI management. These findings highlight key areas for improvement in providing optimal care to patients with CML

Results of a national UK physician reported survey of COVID-19 infection in patients with a myeloproliferative neoplasm

Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/50110000027

Optimisation of CML therapy

TKI inhibitors have revolutionised CML therapy and the goals for management have shifted from finding newer therapies to optimising existing treatment approaches. We have tried to optimise CML therapy by identifying poor responders early by molecular monitoring, improve adherence by using self reported adherence and optimise intolerance by actively changing TKIs to overcome side effects. BCR-ABL PCR of <10% at 3 months and <1% at 6 months have become an accepted standard after the publication by Marin et al. We tried to combine the two measurements and showed that 3 month milestone predicts poor responders and is sufficient to consider changing therapy and that an additional measurement at 6 months does not add any further value. Most existing methods of determining adherence to medications are financially impossible to replicate on a day to day basis or too labour intensive. We tried to measure adherence by 4 different questionnaire based methods (visual adherence scale, Lu’s scale, Haynes method and DAMS scale) and correlate it with clinical responses. We have showed that adherence by all methods correlated with clinical responses and Haynes method which quantifies adherence based on number of doses of medications missed over the last 7 days was the best indicator of adherence amongst all. We further looked at the interactions of daily routine, communication with the physician; access to internet and patients views on taking the medications with adherence to therapy and adherence was shown to be influenced by all of them. Majority of the patients on TKI therapy appeared to be anxious and nearly half of them depressed. Patients with a better QOL had improved adherences. We propose a model based on 4 questions with the most significance on multivariate analysis to be possibly used as a surrogate for adherence methods. It has been shown that intolerance affects adherence and hence outcomes. We have tried to improve intolerance by switching TKI therapy in patients who had attained CCyR and with chronic low grade side effects and showed that the side effects improved and all patients had further improvement in the molecular milestones with deepening responses.Open Acces

A retrospective real-world study of the current treatment pathways for myelofibrosis in the United Kingdom: the REALISM UK study.

Background Myelofibrosis (MF) is a blood cancer associated with splenomegaly, blood count abnormalities, reduced life expectancy and high prevalence of disease-associated symptoms. Current treatment options for MF are diverse, with limited data on management strategies in real-world practice in the United Kingdom. Methods The REALISM UK study was a multi-center, retrospective, non-interventional study, which documented the early management of patients with MF. The primary endpoint was the time from diagnosis to active treatment. Discussion Two hundred patients were included (63% [ = 126/200] with primary MF; 37% [ = 74/200] with secondary MF). Symptoms and prognostic scores at diagnosis were poorly documented, with infrequent use of patient reported outcome measures. 'Watch and wait' was the first management strategy for 53.5% ( = 107/200) of patients, while the most commonly used active treatments were hydroxycarbamide and ruxolitinib. Only 5% of patients proceeded to allogeneic transplant. The median (IQR) time to first active treatment was 46 days (0-350); patients with higher risk disease were prescribed active treatment sooner. Conclusion These results provide insight into real-world clinical practice for patients with MF in the United Kingdom. Despite the known high prevalence of disease-associated symptoms in MF, symptoms were poorly documented. Most patients were initially observed or received hydroxycarbamide, and ruxolitinib was used as first-line management strategy in only a minority of patients. Plain Language Summary Myelofibrosis is a rare blood cancer associated with symptoms that can seriously affect a patient's daily life, such as enlarged spleen and decreased white and red blood cells. Although several treatments are available for patients with myelofibrosis, it is not clear which ones clinicians use most frequently. We aimed to review which treatments are usually given to patients with myelofibrosis in the UK, by collecting information from the medical records of 200 patients with myelofibrosis treated in different centres across the UK. The results showed that the symptoms patients experienced were not always written down in the medical records. Similarly, clinical scores based on patient characteristics (which clinicians use to try to predict if a patient will respond to treatment well or not) were also missing from the medical records. Clinicians also rarely asked patients to complete questionnaires that try to measure the impact of myelofibrosis and its treatment on their health. The most common approach for patients with myelofibrosis in the UK was 'watch and wait', which over half of patients received. The most common drugs used for treatment were hydroxycarbamide and ruxolitinib; only a very small proportion of patients received a bone marrow transplant. On average, patients waited for 46 days before receiving a treatment, although patients considered to have a more aggressive type of disease received treatment sooner. The results of this study suggest that medical records can be missing key information, which is needed to decide which is the best way to treat a patient with myelofibrosis. They also suggest that clinicians in the UK prefer observation to treatment for a large number of patients with myelofibrosis. This could mean that the approach used for many patients with myelofibrosis does not help them to control symptoms that have an impact on their daily lives

Diagnosis and evaluation of prognosis of myelofibrosis: a British Society for Haematology guideline

This document represents an update of the British Society for Haematology (BSH) guideline on myelofibrosis (MF) first published in 2012 and updated in 2015.1 This guideline aims to provide healthcare professionals with clear guidance on the diagnosis and prognostic evaluation of primary myelofibrosis (PMF), as well as post-polycythaemia vera myelofibrosis (post-PV MF) and post-essential thrombocythaemia myelofibrosis (post-ET MF). A section on prefibrotic MF is also included. A separate BSH Guideline covers the management of MF and is published alongside this guideline