First-Line Tagraxofusp Leads to High Response Rates in BPDCN

First-line treatment with tagraxofusp led to an overall response rate (ORR) of 75% in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), according to long-term results from the largest prospective trial evaluating the CD123-targeted therapy in BPDCN.

Naveen Pemmaraju, MD, of the University of Texas MD Anderson Cancer Center, and colleagues conducted the study and published its long-term results with data from the study’s continued access phase in the Journal of Clinical Oncology.

The trial included 84 adults with BPDCN, 65 of whom had not received prior treatment, and 19 of whom had relapsed/refractory (R/R) disease. Patients received tagraxofusp 12 μg/kg once daily. The primary endpoints of the study were complete response (CR) and clinical CR, defined as a CR with residual skin abnormality that is not indicative of active disease.

The objective response rate and ORR were both 75% for treatment-naïve patients at a median follow-up of 34 months. Over half (57%) of treatment-naïve patients achieved a CR plus a clinical CR. The median overall survival (OS) was 15.8 months (95% CI, 9.7-25.8). The median time to remission was 39 days (range, 14-131 days), and the median duration of CR plus clinical CR was 24.9 months (95% CI, 3.8 to not reached).

Researchers reported 19 patients (51%) who achieved CR plus clinical CR were bridged to stem cell transplant. The median CR plus clinical CR duration was 22.2 months (range, 1.5-57.4 months) in those patients. The median OS was 38.4 months (range, 3.4-58.1 months) for patients who received a transplant, with 72% of patients remaining in remission for a year or more after transplant. The survival probability was 66% (95% CI, 43-88) at 24 months.

Of the 18 patients who achieved a CR plus clinical CR but did not receive a transplant, four had responses lasting longer than six months. Researchers reported one patient had a response duration of 27 months, while another had a response duration of 52 months.

The ORR was 58% (95% CI, 33.5-79.7) for patients with R/R disease, including one CR and two clinical CRs. One patient achieved remission and was bridged to transplant. The median time to response was 29 days (range, 21-82 days). The median OS was 8.2 months (95% CI, 4.1-11.9) at a median follow-up of 33.5 months.

The most common adverse events were increased alanine aminotransferase (reported in 64% of patients), increased aspartate aminotransferase (60%), and hypoalbuminemia (51%). Capillary leak syndrome occurred in 21% of patients. Most of the adverse events occurred in the first cycle and were transient.

“These data confirm the efficacy of [tagraxofusp] for the treatment of [first-line] patients with BPDCN and as a rational therapeutic option for patients with R/R disease. [Tagraxofusp] may serve as a bridge to [transplant] in both populations or as induction/maintenance in patients not bridged to [transplant],” the researchers concluded. “The longer treatment durations are an important benefit, as [transplant] may not be a viable path for all patients because of elderly age, comorbid conditions, lack of a donor match, or socioeconomic factors.”

Pemmaraju N, Sweet KL, Stein AS, et al. Long-term benefits of tagraxofusp for patients with blastic plasmacytoid dendritic cell neoplasm. J Clin Oncol. 2022;40(26):3032-3036.