RESEARCH SUMMARY
Study Title: Tagraxofusp, azacitidine, and venetoclax (TAG-AZA-VEN) triplet therapy shows efficacy, tolerability, and transplant potential in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN): Results of a phase 2 trial
Publication: Presented at the 67th American Society for Hematology Annual Meeting and Exposition
Corresponding Dana-Farber Cancer Institute authors: Andrew Lane, MD, PhD
Andrew Lane, MD
Summary: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive blood cancer that has only one approved therapy called tagraxofusp. Most patients relapse after treatment and some experience a severe side effect called capillary leak syndrome that requires close monitoring during and after the five days of dosing in the approved regimen. This phase II study tested a triplet combination of tagraxofusp plus azacitidine and venetoclax in 27 patients with previously untreated or relapsed/refractory BPDCN. According to data from Lane’s lab, azacitidine has the potential to reverse resistance to tagraxofusp and BPDCN is highly sensitive to venetoclax. Based on dosing data from a previous phase 1b study by Lane, the triplet therapy required only 3 days of tagraxofusp.
The triplet therapy was well tolerated with no increased safety concerns compared to tagraxofusp alone or azacitidine and venetoclax combined. Of the 16 previously untreated patients, 88% achieved composite complete responses and 63% went directly to receive allogeneic stem cell transplant. Of the 11 relapsed/refractory patients, 64% achieved composite complete response and 55% went on to receive allogeneic stem cell transplant. Longer follow-up is needed to assess median overall survival for previously untreated patients, who had 1-year and 2-year overall survival of 60%. For relapsed/refractory patients, median overall survival was 8.5 months with 1-year overall survival of 36% and 2-year of 18%. Capillary leak rates were similar or improved compared to the 5-day dosing of single agent tagraxofusp.
Significance: Researchers are searching for ways to improve upon current treatments for BPDCN to deliver more durable responses, enable more patients to proceed to stem cell transplant, and reduce the chances of severe side effects. In this trial, the response rates, the number of patients who went to transplant, and survival appeared similar or possibly better than generally observed with tagraxofusp or azacitidine plus venetoclax (though they were not compared head-to-head). The triplet combination offers a potential new treatment approach for patients with BPDCN that has fewer monitoring requirements and may be similarly or more effective than the previously available options.
Funding: Stemline Therapeutics, Department of Defense