Conference Coverage

‘Very encouraging’ results in BPDCN


Photo from EHA

The 23rd Congress of the European Hematology Association (EHA)

STOCKHOLM—Tagraxofusp (SL-401) has produced “very encouraging” results in a phase 2 trial of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), according to an investigator.

Tagraxofusp, a targeted therapy directed to CD123, produced an overall response rate (ORR) of 83% and a complete response (CR) rate of 62% in patients with previously untreated or relapsed/refractory BPDCN.

Common adverse events (AEs) related to tagraxofusp include hypoalbuminemia, transaminitis, and thrombocytopenia. There was 1 grade 5 AE—a case of capillary leak syndrome (CLS).

Study investigator Naveen Pemmaraju, MD, of The University of Texas MD Anderson Cancer Center in Houston, presented these results at the 23rd Congress of the European Hematology Association (EHA) as abstract S116.

The trial was sponsored by Stemline Therapeutics.

Dr Pemmaraju noted that there are no approved therapies for BPDCN, so patients may be treated with therapies intended for acute myeloid leukemia (AML), acute lymphoblastic leukemia, or lymphomas.

“These are usually quite intense cytotoxic chemotherapy regimens,” he said. “But even with these regimens, most groups report median overall survival times of 8 to 14 months.”

And although stem cell transplants can be effective in BPDCN, a “vast majority” of patients are not fit for transplant, according to Dr Pemmaraju.

With this in mind, he and his colleagues are conducting this trial of tagraxofusp in BPDCN.

The trial has 4 stages. In stage 1, patients received tagraxofusp at 7, 9, 12, or 16 μg/kg on days 1 to 5 of a 21-day cycle. In stages 2 and 3, patients received the drug at 12 μg/kg on days 1 to 5 of a 21-day cycle. Stage 4 is still enrolling.


Dr Pemmaraju presented results in 45 patients—32 with previously untreated BPDCN and 13 with relapsed/refractory BPDCN. The patients’ median age at baseline was 70 (range, 22-84), and 82% were male.

Three patients received tagraxofusp at 7 μg/kg/day, and the rest received the 12 μg/kg/day dose.

Among patients who received the 12 μg/kg/day dose, the ORR was 83% (35/42). The ORR was 90% (26/29) in previously untreated patients and 69% (9/13) in relapsed/refractory patients.

“These are very encouraging results—a 90% overall response rate in the frontline setting,” Dr Pemmaraju noted.

The composite CR rate was 62% (n=26) overall, 72% (n=21) in previously untreated patients, and 38% (n=5) in relapsed/refractory patients.

This included 13 patients with a CR (1 relapsed/refractory), 10 with a clinical CR (3 relapsed/refractory), and 3 with a CR with incomplete hematologic recovery (1 relapsed/refractory). A clinical CR was defined as absence of gross disease with minimal residual skin abnormality.

Fourteen patients went on to stem cell transplant, 1 of whom had relapsed/refractory disease at baseline.

Overall survival results were only available for the 29 previously untreated patients who received tagraxofusp at 12 μg/kg/day. In this group, the median overall survival has not been reached at a median follow-up of 13.8 months (range, 0.2 to 37.4 months).

Dr Pemmaraju said this result is important because it contrasts with the historical expectation of a median overall survival of 8 to 14 months.


Dr Pemmaraju presented safety results in 114 patients who have received tagraxofusp at 12 μg/kg/day on all trials of the drug. These data include patients with AML, myelofibrosis, and chronic myelomonocytic leukemia in addition to the 45 patients with BPDCN. However, AEs were similar regardless of disease.

Common treatment-related AEs (of any grade, occurring in at least 15% of patients) included hypoalbuminemia (49%), ALT increase (48%), AST increase (48%), thrombocytopenia (29%), nausea (27%), pyrexia (25%), chills (23%), fatigue (23%), weight increase (19%), hypotension (18%), peripheral edema (17%), and vomiting (15%).

CLS of any grade was also a common AE, occurring in 20% of patients (n=23). Most cases of CLS were grade 1 or 2, but there were grade 3 (n=5) and 4 (n=2) cases, as well as a single case of grade 5 CLS that occurred in a BPDCN patient.

Dr Pemmaraju did note that CLS has proven manageable with monitoring and pre-emptive measures. Specifically, inclusion criteria were changed so that patients must have normal cardiac function, adequate kidney function, and albumin of at least 3.2 g/dl. Investigators also began monitoring patients’ weight, albumin levels, and kidney function.

“With the combination of greater understanding of CLS, actual definitive protocol adjustments made by investigators, and monitoring, this has been a highly manageable phenomenon,” Dr Pemmaraju said.

Next steps

The investigators plan to continue enrolling patients in this study and collect additional safety and survival data, but Dr Pemmaraju and his colleagues also want to evaluate tagraxofusp in combination with other therapies.

Tagraxofusp is already under investigation in combination with azacitidine in a phase 1/2 trial of patients with high-risk myelodysplastic syndromes and AML.

Dr Pemmaraju is interested in combining hypomethylating agents with tagraxofusp for BPDCN patients as well, to build upon the encouraging results with tagraxofusp alone.

“An extraordinarily rare disease that used to not have any therapies at all now has at least one ongoing clinical trial with some encouraging activity,” he said. “I hope that gives hope to people with rare diseases, to let them know they’re not alone. There may be someone out there who’s researching their disease, no matter how rare it is.”

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