Multinational phase 1-2 trial of pivekimab sunirine in blastic plasmacytoid dendritic cell neoplasm

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare (0.05 cases per 100,000) myeloid malignancy with CD123 interleukin-3 receptor-α overexpression and poor prognosis. A multinational phase 1-2 trial evaluated pivekimab sunirine (PVEK), a novel CD123 antibody-drug conjugate, in adults with frontline (no previous systemtic therapy and de novo BPDCN or coexisting hematologic malignancy) or relapsed/refractory (R/R) BPDCN. The primary endpoint was composite complete response rate (CCR; CR + clinical complete response) in the primary analysis population (PAP; frontline de novo). Of 84 patients, 33 had frontline BPDCN (22 de novo; 11 with previous or concomitant malignancy), and 51 had relapsed/refractory disease; median age was 72 years (range 63-76). In the PAP, the CCR rate was 75% (95% CI 51-91) with a median duration of response 10.6 months, and a median overall survival of 16.6 months (7.2-NR). Eight of these 15 patients proceeded to stem-cell transplant. The corresponding rate for R/R disease was 14% (95% CI 6-27) with a median duration of 9.2 months and a median overall survival of 5.8 months (3.9-8.4). Adverse events included peripheral edema (54%), fatigue (26%), and infusion-related reactions (26%). The authors conclude that PVEK led to high, durable responses, especially in frontline BPDCN, and a manageable safety profile.