Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Risk Stratification and Prognostication
Hematology Disease Topics & Pathways:
Adults, Epidemiology, Age Inequities, Clinical Research, Health Outcomes Research, Health Disparities Research, Clinically Relevant, Real World Evidence, Registries, Equity, Young Adults, Study Population, Diversity, Equity, and Inclusion (DEI), Clinical Practice (e.g. Guidelines, Health Outcomes and Services, and Survivorship, Value; etc.)
Introduction: Myeloproliferative neoplasms (MPNs) – essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) - are associated with significant morbidity and shortened survival, irrespective of age (Srour et al. Br J Hematol. 2016). Despite shortened survival, young MPN patients (pts) are often classified as “low-risk” and managed with aspirin alone, phlebotomy-only (PHL), or observation instead of potentially life-prolonging cytoreductive and/or disease-modifying treatment. Age-biased risk assessment and treatment practices deprive young pts from early intervention and access to clinical trials. Our goal is to highlight the unmet need for identifying and implementing life-prolonging treatment in young MPN pts. Here, we determine and compare the excess mortality from MPNs in young (<60 years) to older pts (≥60 years) in the United States (US).
Methods: In this population-based study, demographic (age, sex, race), survival, and cause-of-death data were collected for MPN pts from the US Survey, Epidemiology, and End Results (SEER) registry between 2001-2017; and for the general US population from the Centers for Disease Control and Prevention Wide-ranging OnLine Data for Epidemiologic Research (CDC WONDER) database. SEER reports cancers classified by International Classification of Diseases for Oncology, version 3 (ICD-O-3), which evolved with the WHO classification of myeloid neoplasms in 2001 for ET, PV and PMF. Cause-of-death is reported by ICD-10 codes, which we categorized into cardiovascular (CVE), second cancers (CA), acute leukemia (AL), and others. Excess, or relative mortality was determined by the ratio of observed mortality in MPN pts (Kaplan-Meier estimate) over the expected mortality of the US population matched by age, sex, race, and birth-year (actuarial estimate). A one-sided log-rank test was used. Excess mortality of young compared to older pts was determined from a random-effects model using restricted maximum-likelihood estimator method. All analyses were performed using RStudio software v 1.4.1106.
Results: The SEER query identified 40,333 MPN pts (ET: 17,420 (43%), PV: 18,027 (45%), PMF: 4,886 (12%)) diagnosed at a median age of 66 years (ET: 67, PV: 65, PMF: 69) of whom 20,470 (51%) were females (ET: 10,709 (61%), PV: 7,768 (43%), PMF: 1,993 (41%)). The 10-year mortality for ET, PV, and PMF pts <60 was 13%, 18%, and 49% respectively (versus 6% for controls); and ≥60 was 59%, 59%, and 87% respectively (versus 35% for controls) (Figure 1A). Excess all-cause mortality was higher in pts <60 compared to ≥60 with ET (2.75 versus 1.82, p<0.001), PV (3.16 versus 1.92, p<0.001), and PMF (10.6 versus 5.73, p<0.001) (Figure 1B). Excess CVE mortality was higher in PV<60 compared to PV≥60 (3.36 versus 2.55, p=0.036) but not in ET or PMF. Excess CA mortality was higher in PV<60 than PV≥60 (2.36 versus 1.53, p=0.002) but not in ET or PMF. Excess AL mortality was high for all pts, particularly PMF, and was not significantly different in pts <60 compared to ≥60
Discussion: Excess or relative mortality emphasizes the burden of MPN-related death with current treatment. In this population-based study, we found excess mortality in young MPN pts (<60), greater than in older pts (≥60). This difference may result from age-biased risk assessment and treatment recommendations that recommend lower intensity therapy for young pts. It may be time to revisit these recommendations since accruing evidence demonstrates long-term safety, efficacy and potential survival benefit of available cytoreductive agents. Certain treatments such as interferon-alpha (IFN) may improve survival in PV (Abu-Zeinah et al. Leukemia. 2021), and a recent randomized clinical trial established superiority of IFN over standard of care PHL in young PV pts (Barbui et al. Lancet Hematol. 2021). These data advocate for early intervention with potentially disease-modifying treatment for all pts regardless of age. These data also call into question age-biased exclusions of many young pts from participation in clinical trials of established or promising drugs.
Conclusion: Excess mortality of young MPN pts (<60) is unacceptably high and greater than that of older pts (≥60). Clinical trials testing early intervention with potentially life-prolonging treatments are required.
Disclosures: Silver: Abbvie: Consultancy; PharamEssentia: Consultancy, Speakers Bureau. Scandura: Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Constellation: Research Funding; MPN-RF (Foundation): Research Funding; CR&T (Foudation): Research Funding; European Leukemia net: Honoraria, Other: travel fees . Abu-Zeinah: PharmaEssentia: Consultancy.
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