BPDCN patients at increased risk of second primary malignancies

June 1, 2020

Rare aggressive cutaneous lymphoma puts patients at risk of thyroid and non-lymphocytic leukemia second primary malignancies, researchers say.

Patients with the rare but aggressive cutaneous lymphoma, called blastic plasmacytoid dendritic cell neoplasm, are at increased risk of thyroid and non-lymphocytic leukemia second primary malignancies. But patients’ overall incidence of second primary malignancies is relatively low, according to a study published April 9 in the Journal of the American Academy of Dermatology (JAAD).1

“Risk of second primary malignancies… in leukemias/lymphomas with cutaneous involvement is a knowledge gap for dermatologists,” the authors wrote. “Overall, our study’s findings may help in surveillance of [blastic plasmacytoid dendritic cell neoplasm] patients, especially as new, lifespan-increasing treatments such as tagraxofusp become available.”

Blastic plasmacytoid dendritic cell neoplasm typically manifests as asymptomatic skin lesions and cytopenias resulting from bone marrow involvement. It presents less commonly in lymph nodes or visceral organs, according to a paper published March 2020 in Current Opinion in Hematology.2

Until recent years, providers often treated patients with intensive chemotherapy regimens, generally reserved for treating acute myeloid leukemia or acute lymphoblastic leukemia, according to the authors of the paper in Current Opinion in Hematology.

Tagraxofusp (tagraxofusp-erzs, Elzonris, Stemline Therapeutics) is an intravenously administered CD123-directed cytotoxin. Tagraxofusp-erzs, which is composed of human interleukin-3 and a truncated diphtheria toxin payload, was FDA approved in late 2018 for the treatment of blastic plasmacytoid dendritic cell neoplasm in adults and pediatric patients, according to the journal Drugs.3

In the JAAD study, researchers at Baylor College of Medicine and the University of Texas MD Anderson Cancer Center Department of Dermatology extracted initial blastic plasmacytoid dendritic cell neoplasm cases from 1973 to 2016 from the Surveillance, Epidemiology, and End Results (SEER) database.

In an average follow-up of 125.37 months, the authors found that 43, or 4.61%, of the 932 cases they identified developed second primary malignancies. Blastic plasmacytoid dendritic cell neoplasm patients were significantly more likely than matched controls without the cancer to develop acute myeloid leukemia, with an excess absolute risk of 7.18. These patients were more likely than controls to develop acute monocytic leukemia, with an excess absolute risk of 1.05. Blastic plasmacytoid dendritic cell neoplasm patients also had a higher risk of thyroid second primary malignancies, with an excess absolute risk of 7.68.

Their analysis showed that thyroid second primary malignancies risk increased more than a year after blastic plasmacytoid dendritic cell neoplasm diagnosis, suggesting the elevated risk for thyroid cancers might be more treatment related from radiation or chemotherapy, rather than incidental or concurrent. The increased risk of nonlymphocytic leukemia suggests a shared etiology, although blastic plasmacytoid dendritic cell neoplasm’s progression to a leukemic phase also could be occurring, according to the study.

“There is a notable lack of lymphoid-origin [second primary malignancies], which supports the current 2008 World Health Organization classification of [blastic plasmacytoid dendritic cell neoplasm] as a subtype of acute myeloid leukemias and related precursor neoplasms,” the authors wrote. “[Blastic plasmacytoid dendritic cell neoplasm] had previously been considered a blastic NK-cell lymphoma but was reclassified based on its plasmacytoid dendritic cell (pDC) origin; however, pDC development is a topic of ongoing research.”

The study is limited by its retrospective design and potential limitations of the data in the SEER database.