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FDA approves pivekimab sunirine for adult patients with BPDCN

On May 27, 2026, the U.S. Food and Drug Administration (FDA) approved pivekimab sunirine (PVEK) for adults with blastic plasmacytoid dendritic cell neoplasm (BPDCN).1

BPDCN is an ultra-rare and aggressive hematologic malignancy arising from abnormal plasmacytoid dendritic cells and often affecting multiple sites, including the skin, bone marrow, peripheral blood, and lymph nodes.2 The disease predominantly affects older adults, with a median age at presentation of 65–70 years, and has historically carried a poor prognosis. To date, limited treatment options have existed for BPDCN, with the only approved agent being tagraxofusp, a CD123-directed cytotoxin.2 While tagraxofusp is highly effective, it can result in severe side effects, such as capillary leak syndrome (CLS), and some patients will develop resistance to the agent, highlighting the need for alternative therapeutic approaches. 2,3  

CD123 is a marker that is universally overexpressed in BPDCN, making it an ideal therapeutic target.2 PVEK has been introduced as a novel CD123-directed antibody-drug conjugate (ADC) that delivers a DNA-alkylating payload to CD123-expressing tumor cells via single-strand DNA breakage. Its mechanism of action may offer reduced toxicity compared to conventional DNA-targeting agents, as it has been designed to spare healthy bone marrow.2

The approval of PVEK is supported by data from the CADENZA trial (NCT03386513), an international Phase I/II, multicenter, open-label, single-arm study evaluating PVEK in 84 patients, aged 63–76 years, without evidence of active central nervous system (CNS) disease.1 Of these patients, 33 were treatment-naïve, and 51 were relapsed/refractory (R/R). PVEK was administered intravenously at 0.045 mg/kg over 15-30 minutes once every 3 weeks until disease progression or unacceptable toxicity.1

Favorable efficacy outcomes were achieved in treatment-naïve patients, with a rate of complete response (CR)/clinical complete response (CRc) of 69.7% (95% CI: 51.3–84.4) at a median follow-up of 21.5 months.1 In R/R patients, the median follow-up was 24.1 months, and a CR/CRc rate of 15.7% (95% CI: 7.0–28.6) was observed. 1 Median duration of CR was 9.7 months (95% CI: 2.9–not estimable) in the frontline group and 9.2 months (Range: 2.7–27.6+) in R/R patients.1 

The safety profile of PVEK was manageable, with the most common adverse events including peripheral edema, fatigue, and infusion-related reactions. Reported Grade ≥3 events included neutropenia, thrombocytopenia, and peripheral edema, as well as low rates of severe adverse events, such as pneumonia and febrile neutropenia. Two cases of veno-occlusive disease (VOD) were observed during treatment with PVEK, with VOD also occurring in five out of 19 patients who proceeded to stem cell transplant.2

At the 2025 American Society of Clinical Oncology (ASCO) Meeting, we spoke with Naveen Pemmaraju, MD, from The University of Texas MD Anderson Cancer Center, Houston, TX, who presented results from the CADENZA trial. Dr Pemmaraju stated, “We conclude from the CADENZA study, PVEK for BPDCN, that we have a novel CD123 ADC targeted agent, well tolerated, that could potentially represent a practice-changing paradigm for our field.”

The approval of pivekimab sunirine marks a significant milestone in the treatment of BPDCN, offering an effective and well-tolerated therapeutic option in both the frontline and R/R setting, with durable responses and the potential to bridge eligible patients to stem cell transplant.

References

  1. U.S. Food and Drug Administration. FDA approves pivekimab sunirine-pvzy for blastic plasmacytoid dendritic cell neoplasm, an ultra-rare hematologic malignancy. Available here. (Last accessed 28/05/2026)
  2. Pemmaraju N, Marconi G, Montesinos P, et al. Pivekimab Sunirine in Blastic Plasmacytoid Dendritic Cell Neoplasm. J Clin Oncol. 2026 Apr;44(10):861-873.
  3. Pemmaraju N, Lane AA, Sweet KL, et al. Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm. N Engl J Med. 2019 Apr;380(17):1628-1637.

Written by Clare Harris

Edited by Natalie Markova