Emerging Combination Strategies and Triplets in BPCDN Treatment

The current research frontier in blastic plasmacytoid dendritic cell neoplasm (BPDCN) is moving toward combination triplet therapies. Andrew A. Lane, MD, PhD, Dana-Farber Cancer Institute, explores the clinical rationale for triplet regimens combining tagraxofusp-erzs (Elzonris), azacitidine (Vidaza), and ventoclax (Venclexta).

Because BPDCN cells are highly BCL-2 dependent for survival, combining venetoclax with hypomethylating agents (HMAs) like azacitidine has shown promising activity even in the relapsed/refractory setting.

Results from a phase 2 trial (NCT03113643) suggested that the combination of tagraxofusp-erzs, azacitidine, and ventoclax may increase both complete response (CR) rates and the number of patients proceeding the transplant compared with tagraxofusp alone. Notably, 63% and 55% of patients in the first-line and relapsed/refractory groups, respectively, proceeded directly to allogeneic stem cell transplant (SCT), including 10 of the 11 patients age 75 or older in the first-line cohort.

The toxicity profile of the tagraxofusp, azacitidine, and venetoclax triplet was as expected and consistent with prior studies, while the rate of capillary leak syndrome (CLS) was equivalent or lower with the triplet than with single-agent tagraxofusp. Laned noted that, as a result, the triplet combination may appear to be an attractive option for older patients who might not tolerate a severe CLS event.