Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) International Registry: Tagraxofusp Cohort Treatment Results

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an orphan malignancy defined by the WHO as affection fewer than 65 per 100,000 people and by the U.S. FDA as affecting less than 200,000 people in the U.S.. The BPDCN international registry was launched in July 2022 with the aim to create a large database for this rare disease, to generate data-driven diagnostic and treatment recommendations, and provide real-world evidence.

Aim: The aim of this abstract is to evaluate the outcomes of BPDCN patients treated with tagraxofusp, an immunotoxin targeting CD123 that was approved by the U.S. FDA in December 2018 and the European EMA in January 2021 for the treatment of BPDCN.

Methods: The registry collects retrospective and prospective data of patients diagnosed with BPDCN after January 1st, 2010. We assessed baseline characteristics, response to treatment and outcomes of BPDCN patients who received tagraxofusp.

Results: As of June 2024, 70 patients from 13 countries (USA, Egypt, Canada, Italy, Georgia, Turkey, UK, India, Armenia, Iraq, Kuwait, Cyprus and Romania) were included in the registry. Among those, 22 patients (from USA, UK and Italy) have received treatment with tagraxofusp. Seventeen patients were treated with tagraxofusp as a first line therapy and 5 patients as a second line. The median age was 76years (range 40-87) with only one female patient. Fifteen patients had received tagraxofusp before the U.S. FDA approval in the setting of clinical trials. In the first line therapy setting, the overall response rate was 82% (14/17 patients) where 9 patients had a complete response (CR), 5 pts partial response (PR), 2 stable disease (SD), and one patient was not evaluable(no information was available). Of the 9 CR patients, 2 passed away from other reasons besides BPDCN, one was lost to follow up, the other 6 relapsed. Median time to relapse was 3 months. Among the relapsed patients, 4 experienced progressive or stable disease on subsequent chemotherapy regimens, 2 were treated with HyperCVAD followed allogeneic stem cell transplantation (allo-SCT) and were alive at last follow-up. Of the 7 patients with PR and SD as first line therapy, 6 experienced progressive disease, 1 patient who was treated with HyperCVAD followed by allo-SCT was alive at last follow-up. None of 5 patients treated with tagraxofusp as a second line therapy experienced CR, two patients experienced short SD, the other three progressive disease. At the last follow-up information was available for 19 of 22 patients of which 4 were alive.

Conclusion: Tagraxofusp yields high response rates with more than 50% CR in the upfront setting; however, the relapse rates without allo-SCT remains high. This therapy is currently only available in selected countries and only 3 out of the 13 countries participating in this registry reported its use. The treatment strategy of BPDCN should be a total therapy approach incorporating novel agents like tagraxofusp with intrathecal chemotherapy and allo-SCT to prevent the relapse.