In the REVEAL study, having high-risk polycythemia vera was associated with lower survival at 4 years compared with low-risk disease.
Patients with high-risk polycythemia vera (PV) had lower survival probability at 4 years compared with patients with low-risk disease, 89% vs 97% (P < .001), respectively, according to findings of the REVEAL study (NCT02252159), the largest prospective and contemporary cohort of patients with PV in the United States.1
“Although the median survival for PV is estimated to be about 20 years, survival in patients with PV has not been evaluated retrospectively,” Carole B. Miller, MD, a hematologist with Ascension Saint Agnes Hospital Cancer Institute in Baltimore, Maryland, said during the presentation at the Society of Hematologic Oncology (SOHO) 2021 Annual Meeting.2 “Granularity with respect to causes of death and patient comorbidities is often lacking,” Miller continued.
REVEAL followed patients with PV who were treated in 227 community and academic practices; the final analysis evaluated the characteristics of deceased patients, survival by risk, and causes of death over the course of the study. Patients were classified as high risk if they were over 60 years of age or had a history of thromboembolic events (TEs) based on modified European LeukemiaNet (ELN) criteria.
Among patients who died (n = 244), the mean age at diagnosis, enrollment, and death was 68.5, 74.5, and 77.1 years, respectively. Among patients who were alive (n = 2266) during the study, median age at diagnosis and enrollment was 60.2 and 65.4 years old, respectively. Patients who died during the study were significantly older at diagnosis and had longer disease duration than patients who were alive, Miller said. The majority of the cohort were males (54.2%), which is consistent with the known demographic data related to PV.
Patients who died during the study had significantly higher symptom burden at enrollment compared with patients who were alive. Among patients who died, the mean myeloproliferative neoplasm-symptom form assessment (MPN-SAF) score was 22.8 (n = 219) and the total symptom score (TSS) over 20 was 50.2%. Among patients who were alive, the MPN-SAF was 18.3 (n = 2008) and the TSS over 20 was 39.0%.
“The MPN-SAF scores were worse for patients who died compared with patients who were alive for fatigue, early satiety, abdominal discomfort, inactivity, bone pain, and unintentional weight loss,” Miller said. “Differences in TSS between patients who died vs alive cohorts were driven by fatigue, early satiety, inactivity, difficulty concentrating, and unintentional weight loss,” she added.
Miller said that the mean MPN, as a total symptom score over time, showed that symptom burden initially increased slightly for enrollment at 3 months, and remained stable thereafter in both cohorts, up to the 30-month post enrollment time period. “Symptom burden increased in patients who had died but remained stable in the patients who were still alive at that time point. Vascular, respiratory neoplasm, gastrointestinal cardiac infections, and injury comorbidities were each significantly more frequent in patients who had died during the study compared with patients who are alive at the end of this study,” Miller continued.
Reviewing comorbidities at enrollment and during follow-up, the investigators noted higher percentages for patients who died vs alive for vascular disorders (72.1% vs 62.3%), respiratory, thoracic, and mediastinal disorders (55.7% vs 33.4%), gastrointestinal disorders (45.1% vs 35.6%), and cardiac disorders (41.0% vs 26.3%).
Investigators observed a significant association between thrombotic events prior to enrollment and during the study period and overall survival. In addition, a significant number of patients had more than 1 elevated hematocrit level or other signs of progressive myeloproliferation in the 6 months before death.
Turning to OS by risk category at enrollment, investigators reported lower survival probability for high vs low-risk patients (TABLE).1
Among patients with a known cause of death (n = 175), the most common cause was vascular complications (33.1%), followed by hematologic malignancy (15.4%), respiratory failure (13.1%), and solid tumor (12.0%). Among patients who died from hematologic malignancy, 9.7% were attributed to acute myeloid leukemia, 3.4% were not specified, and 2.2% were due to myelofibrosis.
“The estimated 4-year mortality over 10% was surprising,” Miller said, “especially given the mean age at enrollment was about 66 years.” Miller concluded, noting that the higher rate of respiratory disorders observed among patients who died, both as comorbidities and causes of death, had not been well characterized in other PV mortality studies. The finding warrants further investigation to determine if some patients with PV may have undiagnosed pulmonary hypertension.
1. Stein BL, Patel K, Scherber R, Yu J, Paranagama D, Miller CB. Mortality and causes of death of patients with polycythemia vera: analysis of the REVEAL prospective, observational study. Presented at: Society of Hematologic Oncology (SOHO) 2021 Annual Meeting. September 8-11, 2021. Abstract MPN-133. https://bit.ly/3jVanoY
2. Alvarez-Larrán A, Pereira A, Cervantes F, et al. Assessment and prognostic value of the European LeukemiaNet criteria for clinicohematologic response, resistance, and intolerance to hydroxyurea in polycythemia vera. Blood. 2012;119(6):1363-1369. doi:10.1182/blood-2011-10-387787