Justin W. Taylor, MD, discusses the evolution of frontline treatment options for patients with blastic plasmacytoid dendritic cell neoplasm, including the integration of tagraxofusp-erzs into the treatment armamentarium in this disease space.
Justin W. Taylor, MD, assistant professor, lab head/PI, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the evolution of frontline treatment options for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), including the integration of tagraxofusp-erzs (SL-401; Elzonris) into the treatment armamentarium in this disease space.
On December 21, 2018, the first-in-class CD123-targeted therapy tagraxofusp gained FDA approval for the treatment of adult and pediatric patients 2 years of age and older with BPDCN.
Prior to this approval, there were no agents specifically approved for the treatment of patients with BPDCN, Taylor begins. Instead, therapeutic approaches utilized in other hematologic malignancies were often applied to BPDCN treatment, he says. This included induction chemotherapy, which is administered in acute myeloid leukemia, or more intensive chemotherapy regimens administered for acute lymphoblastic leukemia, Taylor elaborates. Elderly patients or those who could not tolerate these intensive regimens were treated with a steroid and the antineoplastic agent vincristine, he adds. This regimen is commonly used for treatment in lymphoma.
Several retrospective studies demonstrated that these regimens all provide a median overall survival between 1 and 2 years, indicating the need for better therapeutic options in this disease setting, Taylor notes. The approval of tagraxofusp addressed this unmet need, and provided patients with a unique, targeted approach for BPDCN, he states.
Tagraxofusp consists of the naturally occurring cytokine IL-3, which is linked to a partial diphtheria toxin , Taylor explains. The resulting immunotoxin binds to the IL-3 receptor on CD123-expressing cells with high affinity, and is subsequently brought into the cell through receptor-mediated endocytosis.
The agent’s initial approval was based on efficacy data from the single-arm STML-401-0114 trial (NCT02113982) of patients with BPDCN, Taylor continues. In the pivotal cohort of this trial, patients with treatment-naïve BPDCN receiving tagraxofusp monotherapy had a complete response rate of 53.8%, and median duration of response was not reached at a median follow-up of 11.5 months. An exploratory analysis of the second cohort showed similar response rates for patients with relapsed or refractory BPDCN, supporting the agent’s approval for both patient subsets, Taylor concludes.