Patients With MPNs Face Higher Cardiovascular Risks, in Addition to AML Risk

New data is shedding light on long-term outcomes of patients with BCR/ABL1-negative myeloproliferative neoplasms (MPNs), including the risk of transformation to acute myeloid lymphoma (AML).

The report is based on a comparison of data from the Surveillance, Epidemiology, and End Result (SEER) cancer database to data from a contemporaneous cohort of patients seen at the Mayo Clinic in Minnesota.

The data deal with patients diagnosed with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF).

The national data are based on 10,725 patients with PV, 8768 patients with ET, and 3689 patients with PMF who were diagnosed between 2001-2015.

At a median follow-up of 5.8 years for PV, 5.7 years for ET, and 3.1 years for PMF, the median overall survival for the 3 conditions was 11.9 years (PV), 12.1 years (ET), and 4.0 years (PMF). In terms of progression to AML, 1.0% of patients with PV progressed to AML at a median time of 4.4 years; 1.5% of patients with ET developed AML at a median time of 5.8 years; and 3.3% of patients with PMF were diagnosed with AML at a median time of 2.3 years.

At Mayo, 1952 patients were diagnosed with MPNs between the years 2000-2017. Among the 444 diagnosed with PV, median overall survival was 12.7 years and 2.7% of patients saw AML transformation. A total of 551 patients were diagnosed with ET. They had a median overall survival of 14.9 years and 1.6% experienced AML transformation. Finally, the 957 patients with PMF had a median overall survival of 4.4 years and 9.2% were later diagnosed with AML. The median follow-up for the Mayo cohort was 5.3 years.

Corresponding author Caleb J. Smith, MD, of the Mayo Clinic, said there are 2 possible reasons the Mayo rates of leukemic transformation were higher than the SEER database rates. It could be inaccurate record-keeping or possibly the shorter PMF follow-up time in the SEER database (3.1 years versus 5.3 years). Smith said the latter is more likely.

When the investigators looked at cause-specific mortality, they found a number of different categories of causes, including several types of cancers, cerebrovascular disease, cardiovascular disease, and infections.

Cardiovascular disease (26.1%), solid tumors (12.7%) and myeloid cancer (5%) were common in patients with PV. In patients with ET, cardiovascular disease (25.0%) and solid tumors (12.6%) were similarly common causes of death, though 9.1% of patients with ET died as a result of myeloid cancers. Among patients with PMF, 41.8% of patients had deaths listed in the “other malignancies” category (in situ, benign, or unknown behavior neoplasms and miscellaneous cancers), while 15.9% of patients died of myeloid cancers.

When investigators looked at standardized mortality ratios, they found important insights.

“First, while considered to be a lower risk for leukemic transformation, both PV and ET patients were at 14.3- and 26.3-fold higher observed risk of death from myeloid malignancies compared to the general population,” the authors wrote, adding that the data also show that cardiovascular risk and cerebrovascular risk are also particularly high in patients with PV and ET.

In PMF, in addition to the expected increase in risk of death from myeloid cancers, the investigators also found an increased risk of death from infections and cardiovascular disease.

“This finding is perhaps related to the overall increased morbidity associated with PMF, and should prompt clinicians to address and optimize comorbidities accordingly,” they concluded.

Reference

Smith CJ, Thomas JW, Ruan G, et al. A Population-based study of outcomes in polycythemia vera, essential thrombocythemia, and primary myelofibrosis in the United States from 2001-2015: Comparison with data from a Mayo Clinic single institutional series. Am J Hematol. Published online October 18, 2021. doi:10.1002/ajh.26377