Treatment with tagraxofusp, an anti-CD123 targeted agent previously known as SL-401, appeared to be safe and effective for managing blastic plasmacytoid dendritic cell neoplasm (BPDCN), according to results from a phase II trial presented at the 23rd Congress of the European Hematology Association.
“This disease, with a median overall survival (OS) of eight to 14 months, historically, has no approved standard therapies available,” according to lead study author Naveen Pemmaraju, MD, of The University of Texas MD Anderson Cancer Center in Houston. The results reported with tagraxofusp in this trial are encouraging, he added, especially considering “the side-effect profile we observed, and keeping in mind our patients with BPDCN are at a median age of 70 or older and may not be candidates for intensive chemotherapy.”
The multicenter, open-label, non-randomized trial included 42 patients with either treatment-naïve or relapsed/refractory BPDCN. Patients received tagraxofusp as a daily intravenous infusion of 7 mcg/kg/day, 9 mcg/kg/day, or 12 mcg/kg/day on days one through five of a 21-day treatment cycle. Sixteen patients with either previously untreated or relapsed/refractory disease were included in stage 1 (lead-in) of the trial. Stage 2 (expansion) included 13 patients with either type of disease and stage 3 (pivotal, confirmatory) included 16 patients with treatment-naïve disease; these patients received tagraxofusp 12 mcg/kg, the optimal dose determined in stage 1.
The most common treatment-related adverse events (AEs) reported across the entire patient population were:
- transaminitis (52%)
- hypoalbuminemia (50%)
- thrombocytopenia (38%)
Eight patients (19%) experienced capillary leak syndrome at the highest treatment dose, though the authors noted that this was “generally manageable and reversible.”
Most (90 percent) of patients with treatmentnaïve disease (n=26/29) responded to treatment with tagraxofusp 12 mcg/kg, Dr. Pemmaraju reported (TABLE). This included 21 patients who achieved a combined endpoint of complete response (CR), clinical CR (CRc; absence of gross disease with minimal residual skin abnormality), or CR with incomplete hematologic recovery (CRi).
Stage 3 of this trial met its primary endpoint, with a CR/CRc rate of 54 percent.
The authors also noted that median OS was not reached in treatment-naïve patients.
Based on these results, the manufacturers submitted a biologics license application for tagraxofusp to the U.S. Food and Drug Administration. Tagraxofusp also is being evaluated as a single agent or in combination with other agents for the treatment of chronic myelomonocytic leukemia, high-risk myelodysplastic syndromes, acute myeloid leukemia, multiple myeloma, and myelofibrosis.
The study is limited by its small population, lack of a comparator arm, and lack of data on response duration. However, Dr. Pemmaraju said, “the encouraging single-agent activity seen here is notable. As is the case with many of our treatments in leukemia, the next era of research in BPDCN will need to focus on combinations, such as with hypomethylating agents, cytotoxic chemotherapy, BCL2 inhibitors, and other targeted agents.” He added that more research is needed into “the timing and various modalities of hematopoietic cell transplantation for patients with BPDCN, especially in the era of new targeted agents being investigated.”
The researchers reported no financial conflicts.
Pemmaraju N, Sweet K, Lane A, et al. Results of pivotal phase 2 trial of SL-401 in patients with blastic plasmacytoid dendritic cell neoplasm. Abstract #S116. Presented at the 23rd Congress of the European Hematology Association, June 15, 2018; Stockholm, Sweden.