FDA Approves Pivekimab Sunirine for BPDCN

The FDA has approved the CD123-directed antibody-drug conjugate (ADC) pivekimab sunirine-pvzy (Decnupaz) for the treatment of adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), based on data from the phase 1/2 CADENZA trial (NCT03386513).^1,2

In the treatment-naive cohort of the multicenter, open-label, single-arm CADENZA trial, 23 of 33 patients (69.7%; 95% CI, 51.3%-84.4%) treated with pivekimab sunirine achieved a complete remission (CR) or clinical CR (CRc), with a median follow-up of 21.5 months.³ The median duration of CR/CRc was 9.7 months (95% CI, 2.9-not estimable). Importantly, 13 patients (39.4%) in the treatment-naive group were able to proceed to post-study stem cell transplantation, a clinically meaningful outcome in a disease where bridging to transplant is a key treatment goal. Eleven patients in the frontline treatment group had prior or concurrent cancer diagnoses in addition to BPDCN, making their disease management particularly complex.

Among patients with relapsed or refractory BPDCN—a population with extremely limited salvage options—8 of 51 patients (15.7%; 95% CI, 7.0%-28.6%) achieved a CR or CRc, with a median follow-up of 24.1 months. The median duration of CR/CRc in this group was 9.2 months (range, 2.7-27.6+). Six patients (11.8%) in the relapsed/refractory cohort were also able to receive post-study stem cell transplantation. Published overall survival (OS) data for the relapsed/refractory cohort showed a median OS of 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—outcomes that, while modest in absolute terms, represent meaningful progress in a setting where no approved agents previously existed.³

"BPDCN is an aggressive disease with historically limited therapeutic options, particularly for patients whose disease has relapsed or become refractory. Pivekimab sunirine-pvzy is the first and only CD123-targeting ADC that can be initiated in an outpatient setting, offering a meaningful benefit for BPDCN patients in need of new treatment alternatives," Naveen Pemmaraju, MD, professor of leukemia at The University of Texas MD Anderson Cancer Center, stated in a news release.²

Safety Profile and Boxed Warning

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

The most common adverse reactions occurring in 20% or more of patients were edema, fatigue, musculoskeletal pain, hemorrhage, infusion-related reactions, nausea, and diarrhea. The most common severe laboratory abnormalities included decreased white blood cell counts, decreased platelet counts, decreased red blood cell counts, and elevated blood sugar levels. Clinicians should monitor patients accordingly and may need to delay infusions, reduce doses, or discontinue treatment based on the severity of adverse events.^1,2

CADENZA Study Rationale and Design

CD123 is overexpressed in BPDCN, making it an ideal therapeutic target. Accordingly, the CADENZA trial was designed to evaluate safety, tolerability, pharmacokinetics, immunogenicity, and antileukemia activity, and to determine the maximum tolerated dose, recommended phase 2 dose, and dosing schedule for pivekimab sunirine-pvzy monotherapy. The trial enrolled 2 distinct BPDCN cohorts: treatment-naïve patients (n = 33) and those with relapsed or refractory disease (n = 51), all without evidence of active central nervous system involvement. The primary efficacy end point was the rate of CR or CRc.

The recommended dose of pivekimab sunirine is 0.045 mg/kg administered intravenously over approximately 15 to 30 minutes once every 3 weeks (21-day cycle), calculated based on the patient's actual body weight, and continued until disease progression or unacceptable toxicity. The ability to initiate treatment in an outpatient setting is a clinically meaningful feature for a patient population that has historically required inpatient management for intensive chemotherapy regimens.

BPDCN: A Disease With Limited Options

BPDCN is an ultra-rare and aggressive malignancy that typically affects adult men between the ages of 60 and 70 years. Patients frequently present with skin lesions, and the disease can spread rapidly to the bone marrow, lymph nodes, and central nervous system. Despite intensive chemotherapy, which may include stem cell transplantation, many patients experience relapse, leaving those with relapsed or refractory disease with extremely limited options.

"For patients living with rare cancers, progress in research can be life-changing. This approval delivers a new option for treating BPDCN and demonstrates our determination to drive meaningful advancements for patients affected by difficult-to-treat cancers," Roopal Thakkar, executive vice president of research and development and chief scientific officer at AbbVie, stated in the news release.

REFERENCES

1. US Food and Drug Administration. FDA approves pivekimab sunirine-pvzy for blastic plasmacytoid dendritic cell neoplasm, an ultra-rare hematologic malignancy. May 27, 2026. Accessed May 27, 2026. https://tinyurl.com/2kdkmn6m

2. AbbVie. U.S. FDA approves DECNUPAZ (pivekimab sunirine-pvzy) for treatment of adult patients with blastic plasmacytoid dendritic cell neoplasm, an ultra-rare and aggressive blood cancer with limited treatment options. Press release. May 27, 2026. Accessed May 27, 2026. https://tinyurl.com/2s36fshs

3. 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