Prevalence and Risk Predicators of Secondary Malignancies Among Patients With PV

Key Takeaways:

• Among patients with polycythemia vera (PV), 28% developed at least 1 secondary malignancy, with nonmelanoma skin cancer (NMSC) being the most common nonhematologic cancer.
• Patients who received hydroxyurea before indexing had higher rates of secondary malignancies compared to patients who received phlebotomy.
• In addition to exposure to cytoreductive therapy, age, elevated platelets, and history of cancers were identified as risk predicators of secondary malignancies.

Patients with PV are at increased risk of developing secondary hematologic and nonhematologic cancers, with skin cancers—particularly NMSC—being the most common secondary malignancies.

Using electronic health records from January 2007 to December 2019 taken from Optum Market Clarity, researchers examined prevalence and risk predicators of secondary malignancies among adults with PV.

The study included 20 089 patients with PV, 15.5% of which had cancer before indexing. Among the study population, the median age was 64 years, 57.8% were male, and 88.6% were White.

Prevalence of Secondary Malignancies

After indexing, over one-third (36%) of patients had at least 1 new or ongoing non-PV malignancy, with a prevalence rate of 109.7 events per 1000 patient-years (PY). NMCS was the most common nonhematologic cancer. Prostate and breast cancer were the most common nonskin malignancies.

Among patients who did not have a non-PV malignancy before indexing, 28% developed at least 1 in the postindex period, with an incidence rate of 76 events per 1000 PY. Skin cancer was the most common nonhematologic malignancy, with lung, prostate, breast, and urinary cancers being the most common nonskin cancers.

PV Transformation

Hematologic transformation is a concern in PV management, with patients being at higher risk of developing secondary acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or myelofibrosis (MF).

In the postindex period, rates of AML, MDS, and MF were 0.7 per 1000 PY, 2.8 per 1000 PY, and 14.9 per 1000 PY, respectively. Approximately 6.3% of patients developed MF during the study, 2.8% developed MDS, and less than 1% developed AML.

Risk Factors

The most common risks associated with the development of secondary malignancies include increased age (over 60 years), preindex cytoreductive treatment, elevated platelet and leukocyte counts, and history of cancer.

Among a subset of 17 402 patients with complete medication data, 20.2% received 4 or more weeks of hydroxyurea before indexing, and 19.0% were treated with phlebotomy only.

Patients treated with hydroxyurea were over 2.5 times more likely to develop secondary malignancies compared to those treated with phlebotomy, 140.4 per 1000 PY vs 55.3 per 1000 PY, respectively. Rates of melanoma or NMSC were over 1.5 times higher in the hydroxyurea cohort than the phlebotomy cohort.

Because the association between cytoreductive treatment and secondary malignancies may be explained by disease severity, this data should be interpreted with caution.

Implications for Managed Care

These findings characterize the prevalence and incidence of secondary malignancies among patients with PV, suggesting the need for dermatologic examinations as part of routine clinical practice.

The study also identifies patients with higher risk of developing secondary malignancies, including those over 60 years and those with exposure to cytoreductive therapy.

According to the authors, “Additional prospective studies with longer follow-up times may help provide further clarity on the incidence and risks of secondary malignancies that can occur in the setting of PV, including NMSC, melanoma, and other solid tumors.”

Reference

Pemmaraju N, Markova A, Masarova L, et al. Prevalence, incidence, and risk factors of secondary malignancies in patients with polycythemia vera: a real-world study. Blood Adv. 2026;10(13):4860-4871. doi.org:10.1182/bloodadvances.2025019349