Richard Pazdur, MD
The FDA has approved tagraxofusp-erzs (SL-401; Elzonris) infusion for the treatment of adult and pediatric patients, aged ≥2 years, with blastic plasmacytoid dendritic cell neoplasm (BPDCN).1
The approval is based on data from 2 cohorts of a multicenter, open-label, nonrandomized single-arm trial. In the first cohort, 7 of 13 patients (54%) treated with tagraxofusp achieved a complete remission (CR) or CR with a skin abnormality not indicative of active disease (CRc). In the second cohort, which comprised 15 patients, 1 patient achieved CR and 1 experienced a CRc. Additionally, the median duration of CR/CRc was not reached (range, 3.9-12.2 months).
“Prior to today’s approval, there had been no FDA approved therapies for BPDCN,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, acting director of the Office of Hematology and Oncology Products, in the FDA’s Center for Drug Evaluation and Research. “The standard of care has been intensive chemotherapy followed by bone marrow transplantation. Many patients with BPDCN are unable to tolerate this intensive therapy, so there is an urgent need for alternative treatment options.”
BPDCN is an aggressive and rare disease of the bone marrow and blood that can affect multiple organs, such as lymph nodes and skin. Additionally, it can often present as leukemia or evolve into acute leukemia. The disease is more common in men than women and in patients 60 years and older. Tagraxofusp is directed at the IL-3 receptor, which is overexpressed on cancer stem cells and/or tumor bulk in several hematologic malignancies.
The single-arm trial was comprised of 3 stages. In the lead-in phase, treatment-naïve and relapsed/refractory patients with BPDCN received tagraxofusp IV at 7, 9, or 12 μ/kg daily on days 1 through 5 of a 21-day cycle. Patients with BPDCN who were enrolled in subsequent stages of the study received tagraxofusp at 12 μ/kg, which was dose determined in the lead-in phase. In the expansion phase of the trial, both treatment-naïve and relapsed/refractory patients were included, while the confirmatory phase included only treatment-naïve patients.
The median age was 70 years (range, 22-84) and 82% of patients were male. The median follow-up for all treatment-naïve patients who were treated at 12 μ/kg (n = 29) was 13.8 months (range, 0.2-37.4+).
In the confirmatory phase, prior data showed that this cohort met its primary endpoint with a 54% CR+CRc rate (95% CI, 25.1-80.8).2
Across all stages in treatment-naïve patients who received tagraxofusp at 12 mcg/kg (n = 29), the ORR was 90% with a 72% CR+CRc+CRi rate. Additionally, 45% of treatment-naïve patients treated at this dose were bridged to stem cell transplant. In relapsed/refractory patients, the ORR was 69% with a 38% CR+CRc+CR with incomplete hematologic recovery rate.
Regarding safety, common side effects reported by patients in clinical trials treated with tagraxofusp were capillary leak syndrome, nausea, fatigue, peripheral edema, pyrexia, chills, and weight increase. The most common laboratory abnormalities were decreases in lymphocytes, albumin, platelets, hemoglobin and calcium, and increases in glucose and liver enzymes.
The labeling for tagraxofusp has a boxed warning regarding the increased risk of capillary leak syndrome.
"Today's approval of tagraxofusp is a major step forward for people with BPDCN, their families and the medical community," said Naveen Pemmaraju, MD, associate professor at The University of Texas MD Anderson Cancer Center, and a principal investigator on the tagraxofusp clinical trial. "CD123 is expressed in BPDCN and a number of other hematologic malignancies. The approval of tagraxofusp, a CD123-targeted therapy, represents a new standard of care for patients with BPDCN."
- FDA approves first treatment for rare blood disease. FDA. Published December 21, 2018. https://bit.ly/2V2VD92?rel=0" . Accessed December 21, 2018.
- Pemmaraju N, Lane AA, Sweet KL, et al. Results of pivotal phase 2 clinical trial of tagraxofusp (SL-401) in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). In: Proceedings from the 2018 ASH Annual Meeting; December 1-4, 2018; San Diego, California. Abstract 765.