Three-Drug Treatment Shows Promise for Patients With Rare Blood Cancer BPDCN

A three-drug treatment combination led to high remission rates in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare and aggressive blood cancer, in a phase 2 clinical trial led by researchers at Dana-Farber Cancer Institute.

The findings were recently published in Blood.

The treatment combines tagraxofusp, the first approved drug for BPDCN, with azacitidine and venetoclax. In the trial, 88% of patients who had not been treated before went into remission. Among patients whose disease had returned or resisted earlier treatment, 64% went into remission.

Many patients were then able to move on to allogeneic stem cell transplant while their disease was in remission, an important step that can offer a chance for longer-term disease control.

“BPDCN is a very challenging disease, and patients need better options,” said Andrew Lane, MD, PhD, senior author of the study and Chief of the Division of Hematologic Neoplasia at Dana-Farber. “What is encouraging here is that this regimen showed strong activity in both newly diagnosed and relapsed patients, including many older adults, and helped a substantial number of patients get to transplant in remission.”

BPDCN is a rare cancer of the blood and bone marrow. Its cells carry high levels of a marker called CD123, which tagraxofusp is designed to target. Earlier research from Lane’s lab suggested that BPDCN may also be vulnerable to venetoclax and that azacitidine may help overcome resistance to tagraxofusp. This study tested all three drugs together.

The trial enrolled 27 patients, with a median age of 70. Sixteen were receiving their first treatment for BPDCN, and 11 had relapsed or refractory disease.

The results were especially encouraging in the newly diagnosed group. Median overall survival and progression-free survival had not yet been reached at the time of analysis. At two years, 65% of those patients were still alive, and 53% had no disease progression. In the relapsed or refractory group, median overall survival was 8.4 months.

The regimen also appeared manageable from a safety standpoint. A known side effect of tagraxofusp called capillary leak syndrome occurred in 15% of patients and was mostly mild to moderate.

Researchers also noted that the regimen used three days of tagraxofusp, rather than the longer standard schedule used when the drug is given alone, while still showing strong activity.

“This is a rare cancer, so it is meaningful to see this level of response in both the front-line and relapsed settings,” Lane said. “The combination appears to build on what tagraxofusp can do alone and may offer a new option for patients who urgently need more effective therapies.”