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917 Prospective Symptom Burden Analysis in 784 Patients with Myeloproliferative Neoplasms: High Burden Correlates with Inflammatory/Genetic Biomarkers and Reduced SurvivalClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 906. Outcomes Research – Myeloid Malignancies: Symptom Burden and Supportive Therapies
Hematology Disease Topics & Pathways:
Research, adult, Clinical Research, health outcomes research, real-world evidence, registries, young adult , Study Population, Human
Monday, December 11, 2023: 3:45 PM

Alisa Poullet, MD1*, Lambert Busque, MD2,3,4, Shireen Sirhan, MD, FRCP3,5, Robert Delage, MD, MSc3,6, Ghislain Cournoyer, MD3,7, Ines Chamakhi, MD3,8, Danielle Talbot, MD3,9*, Luigina Mollica, MD, PhD2,3,4*, Daniele Marceau, MD3,10, Vincent Ethier, MD, BSc3,11, Pierre Desjardins, MD3,12*, Harold J. Olney, MD3,4,13, Michaël Harnois3* and Natasha Szuber, MD, MSc2,3,4

1Department of Internal Medicine, University of Montreal Hospital Center, Montréal, QC, Canada
2Department of Hematology, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada
3Quebec CML-MPN Research Group, Montreal, QC, Canada
4University of Montreal, Montreal, QC, Canada
5Segal Cancer Center, Jewish General Hospital, Montreal, QC, Canada
6Integrated Cancer Center, CHU de Québec, Laval University, Quebec, QC, Canada
7Hemato-oncology, St-Jérôme Hospital, Saint-Jerome, Canada
8Hemato-oncology, Hôpital du Sacré-Cœur de Montréal, Montreal, QC, Canada
9Hemato-oncology, Cité-de-la-Santé Hospital, Laval, QC, Canada
10Hemato-oncology, Hôtel-Dieu de Lévis, Quebec, QC, Canada
11Sherbrooke University Hospital Center (CHUS), Sherbrooke University, Sherbrooke, QC, Canada
12Hemato-oncology, Charles-Lemoyne Hospital, Sherbrooke University, Sherbrooke, Canada
13Department of Hematology, University of Montreal Hospital Center, Montreal, QC, Canada


Myeloproliferative neoplasms (MPN) are associated with significant symptom burden, influencing patient quality of life and management. Thorough assessment of this burden is crucial; however, data from large populational registries are limited. Our objective was to characterize symptom burden in a large MPN cohort, determining: i) age-associated differences; ii) treatment effect; iii) biologic correlatives, and iv) impact on overall survival (OS) in a large, real-world population based setting.


This is a multicenter prospective study analyzing patient-reported outcomes per MPN-Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), a validated questionnaire grading (0-10) ten MPN symptoms (JCO, 2012). Recruitment: Quebec CML-MPN Research Group registry (>20 community/academic centers). Eligibility: i) diagnosis of polycythemia vera (PV), essential thrombocytosis (ET), or myelofibrosis (MF) per WHO criteria; ii) completion of 1+ MPN-SAF TSS between 2013-2022. Conventional statistics were used (JMP® Pro 14.1.0 software; SAS Institute, NC, USA).


4105 MPN-SAF TSS were completed by 784 patients (n= 285 PV, n=422 ET, n=77 MF). Median age at diagnosis was 63 years (range 19-96); female preponderance (56%). A median of 5 questionnaires were completed/patient (range 1-16). Mean symptom score was 16.7 (+/-12.3). A clinically significant total score, defined as >20, was reported by 33% of patients (n=261); most frequently women (p<0.0001) and MF cases (p=0.03).

Symptom burden in the young: N=74 (9%) were age <40 years at diagnosis. At recruitment, mean aggregate and maximum MPN-SAF TSS scores were comparable across younger and older subsets (p=0.3-0.9) (Table 1), despite lower risk scores in the former (p<0.05). When scores were deconstructed, younger patients - vs older, had significantly higher levels of fatigue (p=0.03) and abdominal pain (0.007).

Impact of therapy: Of those with high MPN-SAF scores, a considerable proportion were not treated (n=69/179, 39%). Higher mean scores were also reported in those having initiated therapy >36 months from diagnosis (p=0.0009). Of those with available MPN-SAF pre/post treatment, 37% showed deteriorating scores following cytoreduction, regardless of agent (p=0.4). Notably, those not on antiplatelet therapy had significantly higher mean (p=0.0006) and sub-item scores (excluding fever/night sweats). Over time, all interventions confounded, n=338 (43%) experienced worsening of MPN-SAF scores.

Clinical biomarkers: Patients with anemia (hemoglobin <100 g/L) had significantly higher mean MPN-SAF scores and worse fatigue, inactivity, concentration, bone pain, and weight loss (all p<0.05). Increased C reactive protein (CRP) associated significantly with higher MPN-SAF scores (p=0.03), as well as fatigue, inactivity, early satiety, and bone pain (all p<0.05). Notably, patients with JAK2V617F variant allele frequency >50% (VAF) had higher average (p=0.03) and maximum (p=0.001) MPN-SAF, higher inactivity scores (p=0.02), and more frequent worsening scores over time (p=0.05).

Survival impact: Higher mean MPN-SAF score had a significantly detrimental impact on OS (p=0.05) (Figure 1). Multivariate analysis revealed absence of antiplatelet therapy, age at diagnosis >65 years, male sex, and high-level inactivity to be independent predictors of inferior OS (HR 29, 6, 3 and 3 respectively).


This is a large-scale study comprehensively appraising symptom burden in MPN patients, disclosing several novel findings. First, it unexpectedly exposes disproportionately severe symptoms (fatigue/abdominal pain) in younger patients. Second, it reveals deterioration of symptoms in the face of therapy in a significant number of patients, underscoring inadequacy of current therapies in symptom control. Third, it discloses anemia, elevated CRP, and JAK2 VAF>50% as putative biomarkers of symptom burden; potential adjuncts in identifying highly symptomatic subsets, particularly in situations where symptom assessment is challenging. Finally, it confirms negative survival impact of high symptom burden in a real-world setting. Overall this data exposes a critical unmet need for new therapeutic avenues aimed at alleviating symptom burden in patients with MPN. Further delineation of the inflammation-symptom relationship and future studies using novel prevention strategies are warranted.

Disclosures: Busque: Novartis: Honoraria; BMS: Honoraria; Taiho: Honoraria; Paladin: Honoraria. Sirhan: Novartis: Honoraria, Research Funding; GSK: Honoraria. Olney: Amgen Canada: Honoraria; Bristol Myers Squibb Canada: Honoraria; Novartis Canada: Honoraria; Taiho Canada: Honoraria; Sobi Canada: Research Funding.

*signifies non-member of ASH