Tagraxofusp led to a 90% overall response rate as a first-line therapy in patients with blastic plasmacytoid dendritic cell neoplasm.
Naveen Pemmaraju, MD
Tagraxofusp (SL-401; Elzonris) led to a 90% overall response rate (ORR) as a first-line therapy in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), according to prospective results of a nonrandomized phase II trial that were published in the New England Journal of Medicine.1
Specifically, in patients who received frontline tagraxofusp at 12 μg/kg, the combined rate of complete response (CR) and clinical CR in patients who had not had prior therapy, which was the study’s primary endpoint, was 72%. Responses were observed regardless of whether or not patients received prior lines of treatment.
“In adults with BPDCN, tagraxofusp led to clinical responses regardless of whether patients had received previous therapy,” lead study author Naveen Pemmaraju, MD, an associate professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, said in a press release.2 “We observed high response rates including an overall response rate of 90% among frontline-treated patients. These findings offer hope for patients who have had no treatments specific to this disorder.”
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.
In December 2018, the FDA approved tagraxofusp-erzs infusion for the treatment of adult and pediatric patients, aged ≥2 years, with BPDCN. Tagraxofusp targets the cell surface receptor CD-123, which is expressed in BPDCN and other hematologic malignancies.
The approval was based on the findings from these 2 cohorts of the multicenter, open-label, nonrandomized single-arm phase II trial (NCT02113982). The open-label, multicenter, multicohort trial is said to be the largest of its kind and enrolled 47 adult patients who had been diagnosed with BPDCN between 2014 and 2017. Investigators administered tagraxofusp at 7 μg or 12 μg/kg on days 1 to 5 of each 21-day cycle in the frontline (n = 32) or relapsed/refractory setting (n = 15). Treatment was administered until disease progression or unacceptable toxicity.
The study comprised 3 stages: a 3+3 design to identify the recommended phase II dose (stage 1), a phase to evaluate efficacy and further determine the safety profile of tagraxofusp in a larger patient population at the recommended dose of 12 μg/kg (stage 2), and a confirmatory study design to validate efficacy in a pivotal cohort of patients who received no prior treatment (stage 3).
To be eligible for enrollment, patients had to have an ECOG performance score of 0 to 2 and adequate organ function. Those who had received chemotherapy or other investigational treatment 2 weeks prior to enrollment, had clinically significant active cardiopulmonary disease, or who were receiving immunosuppressive therapy at the time of enrollment were excluded.
The primary endpoint was the combined rate of CR and clinical CR in patients who had not had prior therapy; a key secondary endpoint was duration of response (DOR).
In the previously untreated cohort, the median age was 68 years (range, 22-84), and 81% of patients were male compared with 72 years (range, 44-80) and 87% men in the relapsed/refractory group. Also, in the previously treated subgroup, 9 patients (60%) received 1 prior therapy, 4 (27%) received 2 or 3 lines, and 2 patients (13%) received ≥4 lines of therapy.
Disease presentation at baseline was similar regardless of prior therapies. Ninety-four percent of the overall population had disease manifestations in skin disorders, 51% in bone marrow, 45% in lymph nodes, 17% in peripheral blood, and 17% in visceral sites.
At a median follow-up of 13.8 months, 13 patients were assessed for the primary endpoint and were enrolled in stage 3 of the trial, in which the combined rate of CR and clinical CR was 54% (95% CI, 25%-81%).
Results also showed that among the 29 patients who received first-line tagraxofusp at 12 μg/kg, 45 patients were able to undergo stem cell transplantation. The 8- and 24-month OS rates were 59% and 52%, respectively. The median time to response was 43 days (range, 14-131), and the median DOR was not reached.
In patients who received tagraxofusp in the relapsed/refractory setting, the ORR was 67% and the median OS was 8.5 months.
Those who received the 7-μg/kg dose (n = 3) of tagraxofusp were not included in the efficacy analysis.
Regarding safety, the most common adverse events (AEs) were increased levels of alanine aminotransferase (64%), aspartate aminotransferase (60%), hypoalbuminemia (55%), peripheral edema (51%), and thrombocytopenia (49%). Capillary leak syndrome occurred in 19% of patients and was linked with 1 death in each dosage cohort.
Tagraxofusp is also being investigated in clinical trials for chronic myelomonocytic leukemia and myelofibrosis.