Dr Pemmaraju on Responses With Pivekimab Sunirine in Frontline and R/R CD123+ BPDCN

“We're now working on the late-stage development of pivekimab sunirine, and we hope that this agent can continue to open up the field of CD123-targeted therapy.”

Naveen Pemmaraju, MD, a professor of medicine and chief of the Section of Myeloid Malignancies at The University of Texas MD Anderson Cancer Center, discussed the therapeutic potential of pivekimab sunirine (IMGN632) in CD123-positive blastic plasmacytoid dendritic cell neoplasm (BPDCN) based on data from the phase 2 CADENZA trial (NCT03386513).

BPDCN is a rare and aggressive hematologic malignancy with a historically limited treatment arsenal comprising a single FDA-approved CD123-targeted therapy: tagraxofusp, which was approved in 2018.

The CADENZA trial evaluated pivekimab sunirine at the recommended phase 2 dose of 0.045 mg/kg every 21 days in 84 patients with CD123-positive BPDCN. Thirty-three patients were treatment-naive (median age, 73 years; ≥65 years, 91%); 51 had relapsed or refractory disease (median age, 69 years; ≥65 years, 59%). Patients in the relapsed/refractory cohort had received 1 to 3 prior systemic regimens, with 57% having received prior tagraxofusp. The median follow-up was 21.5 months in the frontline group and 24.1 months in the relapsed/refractory group.

In the frontline cohort, the complete remission (CR) plus clinical CR (CRc) rate was 70% (95% CI, 51.3%-84.4%), with a median CR/CRc duration of 9.8 months (95% CI, 4.6–not reached). The overall response rate (ORR) was 85%, and the median overall survival (OS) was 16.6 months (95% CI, 11.4–not reached). Although outcomes in the relapsed/refractory cohort were not detailed in this discussion, Pemmaraju noted that efficacy signals in this population remain an area of ongoing investigation.

The potential approval of pivekimab sunirine would represent a significant expansion in the targeted therapy arsenal for BPDCN., Pemmaraju continued He noted that differing toxicity profiles between pivekimab sunirine and existing agents could allow for individualized therapy selection, potentially improving tolerability while preserving efficacy. The availability of an additional therapeutic option could enable clinicians to sequence treatments more strategically in both the frontline and relapse settings, offering opportunities for deeper and longer-lasting remissions.

Placing these findings in the broader context of rare disease oncology, Pemmaraju underscored the importance of continued drug development regardless of disease prevalence. For ultra-rare malignancies such as BPDCN, even incremental therapeutic advances can meaningfully impact patient care, he concluded.