According to a multi-center trial, the targeted therapy tagraxofusp induced high response rates among patients with the rare blood cancer blastic plasmacytoid dendritic-cell neoplasm (BPDCN).

The trial results, published in the New England Journal of Medicine, supported the FDA approval of tagraxofusp last December.

“The exact incidence of BPDCN is unknown but may represent 0.5% of all hematologic cancers,” Andrew Lane, MD, PhD, co-first author of the paper and director of Dana-Farber’s BPDCN Center, and colleagues wrote. “Outcomes with conventional treatments that are modeled after therapies for acute leukemia and lymphoma have been disappointing. Patients who undergo allogeneic or autologous stem-cell transplantation during first remission often do well, but traditional chemotherapy has been associated with rates of early death of 17 to 26% and high relapse rates."

Cancer cells. Source: Getty

Almost all patients with BPDCN overexpress interleukin-3 receptor subunit alpha (IL3RA or CD123). Tagraxofusp is a CD123-directed directed cytotoxin which is approved to treat BPDCN.

In the open-label study, researchers assigned 47 patients (median age, 70 years; range, 22-84) with previously untreated (n = 32) or relapsed (n = 15) BPDCN to receive the targeted therapy. Dosing consisted of 7 μg or 12 μg per kilogram of body weight on days 1 to 5 of each 21-day cycle. Treatment continued until disease progression or unacceptable toxic effects.

Among the 29 previously untreated patients who received tagraxofusp at a dose of 12 μg/kg, researchers observed a combined rate of complete response and clinical complete response among 72% (n = 21) of patients. The overall response rate among this subset of patients was 90%, where 45% went on to undergo stem-cell transplantation. For these 29 patients the overall survival at 18 months was 59% and 52% at 24 months.

“The response rate to this drug was quite high, particularly in patients who had not previously been treated,”  Lane said in a press release.

Among the 15 previously-treated patients, the response rate was 67% and the median overall survival was 8.5 months.

The most common adverse events included increased levels of alanine aminotransferase (64%) and aspartate aminotransferase (60%), hypoalbuminemia (55%), peripheral edema (51%), and thrombocytopenia (49%). Researchers saw capillary leak syndrome among 19% of the patients and and it was associated with one death in each of the dose subgroups.

“We treated patients up to the age of mid-80s, and there was no obvious difference in toxicity by age, which is not the case in standard chemotherapy,” said Lane. “Unlike standard chemotherapy, there doesn’t seem to be a cumulative toxicity with this drug. In fact, its side effects are most prominent in the first treatment cycle.”

“We can celebrate this new drug; it’s great to have approval,” Lane added. “Still, we continue to work on improving outcomes for patients.”