FDA Approves Pivekimab Sunirine for Blastic Plasmacytoid Dendritic Cell Neoplasm

The FDA has approved pivekimab sunirine-pvzy (Decnupaz) for the treatment of adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The regulatory decision was backed by data from the phase 1/2 CADENZA trial (NCT03386513), which showed that at a median follow-up of 21.5 months, treatment-naive patients with BPDCN (n = 33) experienced a complete remission/clinical complete remission (CR/CRc) rate of 69.7% (95% CI, 51.3%-84.4%) and a median duration of CR/CRc of 9.7 months (95% CI, 2.9-not estimable [NE]).

Furthermore, at a median follow-up of 24.1 months, patients with relapsed/refractory BPDCN (n = 51) achieved a CR/CRc rate of 15.7% (95% CI, 7.0%-28.6%) and a median duration of CR/CRc of 9.2 months (range, 2.7 to 27.6+).

What is pivekimab sunirine?

Pivekimab sunirine is a first-in-class antibody-drug conjugate that features a high-affinity anti-CD123 antibody, a cleavable linker, and an indolinobenzodiazepine pseudodimer payload.² The payload is intended to alkylate DNA and yield single-strand DNA breaks without crosslinking.

How was the CADENZA trial conducted?

CADENZA was an open-label, multicenter, phase 1/2 trial that enrolled patients at least 18 years of age with BPDCN, with CD123 positivity confirmed by flow cytometry or immunohistochemistry. The study included patients with de novo BPDCN or patients with a prior or concomitant hematologic malignancy (PCHM) who had not received systemic therapy, along with patients with relapsed/refractory BPDCN who received 1 to 3 prior systemic therapies.

After the study evaluated 2 different dosing schedules in dose escalation, the dose-expansion portion of the trial looked at pivekimab sunirine administered at 0.045 mg/kg and 0.090 mg/kg once every 3 weeks. The recommended phase 2 dose of pivekimab sunirine was 0.045 mg/kg once every 3 weeks, and this is the recommended dosage accompanying the FDA approval.^1,2

CR/CRc rate served as the trial’s primary end point.²

What additional efficacy data were reported from CADENZA?

Findings published in the Journal of Clinical Oncology showed that among the de novo and PCHM population (n = 33), the median overall survival (OS) was 16.6 months (95% CI, 11.4-not reached [NR]); the 12- and 18-month OS rates were 64% (95% CI, 44.9%-77.5%) and 44% (95% CI, 26.7%-60.3%), respectively. Notably, in patients with de novo PBDCN (n = 20), the median OS was 16.6 months (95% CI, 7.2-NR), with respective 12- and 18-month OS rates of 60% (95% CI, 35.7%-77.6%) and 49% (95% CI, 26.0%-68.6%).

For patients with relapsed/refractory BPDCN (n = 33), the median OS was 5.8 months (95% CI, 3.9-8.4), with 12- and 18-month OS rates of 31% (95% CI, 18.2%-44.1%) and 19% (95% CI, 8.9%-32.7%), respectively.

What safety data have been reported for pivekimab sunirine?

The prescribing information for pivekimab sunirine includes a boxed warning for hepatotoxicity, including hepatic veno-occlusive disease, and warnings and precautions for infusion-related reactions, edema, sulfite allergic reactions, and embryo-fetal toxicity.¹

Safety data from CADENZA published in the Journal of Clinical Oncology showed that among evaluable patients (n = 84), adverse effects (AEs) led to dose delays in 25% of patients, dose reductions in 5% of patients, and treatment discontinuation in 13% of patients.²

Any-grade AEs occurred in 99% of patients, including 73% who had treatment-related AEs (TRAEs). The rates of grade 3 or higher AEs and TRAEs were 79% and 36%, respectively. The respective rates of any-grade serious AEs and serious TRAEs were 51% and 24%.

The most common any-grade AEs reported in at least 20% of patients included peripheral edema (54%), fatigue (26%), infusion-related reaction (26%), nausea (20%), and hypokalemia (20%).

References

1. FDA approves pivekimab sunirine-pvzy for blastic plasmacytoid dendritic cell neoplasm, an ultra-rare hematologic malignancy. FDA. May 27, 2026. Accessed May 27, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pivekimab-sunirine-pvzy-blastic-plasmacytoid-dendritic-cell-neoplasm-ultra-rare
2. Pemmaraju N, Marconi G, Montesinos P, et al. Pivekimab sunirine in blastic plasmacytoid dendritic cell neoplasm. J Clin Oncol. 2026;44(10):861-873. doi:10.1200/JCO-25-02083