CONTEXT:Blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic malignancy with poor prognosis, is characterized by clonal expansion of plasmacytoid dendritic tumor cells expressing specific markers including the interleukin-3 receptor alpha (CD123). Tagraxofusp (TAG) is a CD123-targeted therapy approved by the FDA and EMA. A global expanded access program (EAP) was implemented prior to TAG's EMA authorization to provide access to patients in real-world practice.
OBJECTIVE:Main objectives were rates of complete response and incidence/severity of capillary leak syndrome (CLS). Key secondary objectives included rate of patients bridged to transplantation, survival, safety, number of cycles administered.
DESIGN:Non-interventional, retrospective analysis of BPDCN patients enrolled in the European EAP from 08.2019-12.2021.
SETTING:57 European centers (Germany, France, Italy, Switzerland, United Kingdom, Spain, Austria).
PATIENTS:76 adult (median age 64 years, range 21-85 years) and 4 pediatric patients with BPDCN confirmed by hematopathology with established marker panels (including CD123).
INTERVENTIONS:TAG 12 mcg/kg was administered intravenously once daily on days 1-5 (up to day 10 allowed) of a 21-day cycle. Hospitalization was required for the first cycle (subsequent cycles allowed outpatient administration).
MAIN OUTCOME MEASURES:Review of case report forms and individual records of patients who met criteria for TAG prior to regulatory approval.
RESULTS:Most patients were male (78%), representing real-world distribution. Sixty-three patients received TAG first-line and 17 patients as second/or further line of treatment. The median number of cycles was 2.5 (range 1-8) in first-line and 2.6 (range 1-13) in second-line/further, respectively. No deaths due to CLS were reported. Adverse events (AEs) mainly occurred in cycle 1, with similar rates and severity in older vs younger patients. Analysis is ongoing; data on safety, efficacy, transplantation, and time-related parameters will be reported.
CONCLUSIONS:The is the largest retrospective analysis of real-world clinical practice outside of a clinical trial in BPDCN patients treated with TAG. Adherence to the EAP and multidisciplinary training is thought to have positively affected prevention and management of CLS and other grade 3-4 AEs. These preliminary results confirm the feasibility and safety of TAG, including in elderly patients, with manageable safety.