In a landmark advancement for patients with ultra-rare blood cancers, the U.S. Food and Drug Administration (FDA) has approved pivekimab sunirine (Decnupaz™; AbbVie), previously known as IMGN632, marking the first and only antibody-drug conjugate (ADC) authorized for the treatment of adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).[1]
This approval introduces a new outpatient-initiated option for a disease where effective therapies have long been elusive.
A New Era for BPDCN Treatment
BPDCN is a highly aggressive and rare hematologic malignancy, with CD123 interleukin-3 receptor-α overexpression, affecting an estimated 500 to 1,000 people annually in the U.S., most often adult men aged 60 to 70. The disease typically presents as skin lesions but can rapidly progress to involve the bone marrow, lymph nodes, and central nervous system. Initial treatment often involves intensive chemotherapy and stem cell transplantation, or tagraxofusp (Elzonris®; Stemline Therapeutics, a Menarini Group Company), yet relapses are common, and prognosis remains poor.
“For patients living with rare cancers, progress in research can be life‑changing,” said Roopal Thakkar, M.D., executive vice president and chief scientific officer at AbbVie.
“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,” Thakkar noted.
Pivekimab sunirine, a targeted innovation
Pivekimab sunirine is a CD123-directed ADC, uniquely engineered to deliver a potent cell-killing agent directly to BPDCN cells. CD123 (IL-3Rα) is overexpressed on BPDCN cells, making it an ideal therapeutic target. It comprises a high-affinity CD123 antibody, a cleavable linker, and a novel indolinobenzodiazepine pseudodimer payload*. Upon binding to these cells, pivekimab sunirine releases an indolinobenzodiazepine payload that induces single-strand DNA breaks, triggering apoptosis.
This approval also marks AbbVie’s first ADC for blood cancer, reflecting the company’s broader commitment to developing targeted, transformative therapies for hard-to-treat malignancies. Studies are ongoing in (pediatric) acute myeloid leukemia (AML). Researchers at the Fred Hutchinson Cancer Center in Seattle are planning to conduct a phase 1 trial (NCT06034470) to find the best dose of pivekimab sunirine when given together with fludarabine, cytarabine, granulocyte colony-stimulating factor (G-CSF), and idarubicin, (FLAG-Ida) regimen. This study will also investigate the effectiveness of this combination therapy in treating patients with newly diagnosed adverse risk acute myeloid leukemia (AML) and other high-grade myeloid neoplasms.
Other ongoing and scheduled studies include the Phase 2/3 Rivival Study (NCT07581002) designed to assess the adverse events and changes in the disease activity when pivekimab sunirine is given in combination with venetoclax and azacitidene in adult participants with AML ineligible to receive intensive chemotherapy.
CADENZA Trial: Efficacy and Safety
The FDA’s decision was based on the pivotal Phase 1/2 CADENZA trial (NCT03386513) , a multicenter, open-label, single-arm study evaluating pivekimab sunirine in adults with BPDCN. The trial enrolled both newly diagnosed (n=33) and relapsed/refractory (n=51) patients, all of whom were without active central nervous system involvement. Efficacy was based on the rate of complete remission or clinical complete remission (CR/CRc).
Study Results:
In Newly Diagnosed Patients:
- 23 patients (69.7%; 95% CI: 51.3, 84.4) achieved a CR/CRc with a median follow-up of 21.5 months.
- The median duration of CR/CRc was 9.7 months (95% CI: 2.9, not estimable).
- 39.4% proceeded to post-study stem cell transplantation.
In relapsed or Refractory Patients:
- 8 patients (15.7%; 95% CI: 7.0, 28.6) achieved a CR/CRc with a median follow-up of 24.1 months.
- The median duration of CR/CRc was 9.2 months (Range: 2.7, 27.6+).
- 11.8% proceeded to post-study stem cell transplantation
“BPDCN is an aggressive disease with historically limited therapeutic options, particularly for patients whose disease has relapsed or become refractory,” noted Naveen Pemmaraju, M.D., professor of leukemia at The University of Texas MD Anderson Cancer Center.
“Pivekimab sunirine 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,” Pemmaraju added.
Safety Profile and Boxed Warning
The most common adverse reactions observed in at least 20% of patients included edema, fatigue, musculoskeletal pain, bleeding, infusion-related reactions, nausea, and diarrhea. Pivekimab sunirine carries a boxed warning for hepatotoxicity, specifically hepatic veno-occlusive disease—a potentially life-threatening liver complication. Additional warnings include risks of infusion-related reactions, edema, sulfite allergic reactions, and embryo-fetal toxicity.
Patients are closely monitored with blood tests before and during treatment to detect liver issues early. Infusion-related reactions are managed with premedication and careful observation during and after administration.
Dosing and Administration
Pivekimab sunirine is administered intravenously at 0.045 mg/kg over 15-30 minutes every three weeks, calculated based on actual body weight, and can be started in an outpatient setting—an important consideration for patient quality of life.
Regulatory Milestones
The FDA granted Pivekimab sunirine priority review, breakthrough therapy, and orphan drug designation, recognizing the urgent need for effective therapies in BPDCN and the drug’s potential to offer significant benefit over existing treatments.
AbbVie’s approval of pivekimab sunirine underscores the company’s focus on advancing standards of care in oncology, particularly for rare and hard-to-treat cancers. With a robust pipeline encompassing more than 35 investigational medicines for blood and solid cancers, AbbVie continues to develop targeted therapies designed to disrupt cancer cell growth and survival.
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Note: * The payload, FGN849, is a member of the indolinobenzodiazepine pseudodimer (IGN) class of cytotoxic drugs. It is an organic molecule described by its chemical structure: [(2S)-2-[[[4-(aminomethyl)phenyl]amino]methyl]-4-methyl-1,3-thiazol-5-yl]-(2-methylidenebenzoic acid).
Clinical trials
Study of IMGN632 in Patients With Untreated BPDCN and Relapsed/Refractory BPDCN – ClinicalTrials.gov ID NCT03386513
Combination Chemotherapy (FLAG-Ida) With Pivekimab Sunirine (PVEK) for the Treatment of Newly Diagnosed Adverse Risk Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms – ClinicalTrials.gov ID NCT06034470
A Study to Assess Adverse Events and How Intravenous (IV) Pivekimab Sunirine Moves Through the Body in Pediatric Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) – ClinicalTrials.gov ID NCT07306832
Highlights of Prescribing Information
Pivekimab sunirine (Decnupaz™; AbbVie)[Prescribing Information]
Medication Guide
Pivekimab sunirine (Decnupaz™; AbbVie)[Medication Guide]
Reference
[1] Daver NG, Montesinos P, DeAngelo DJ, Wang ES, Papadantonakis N, Todisco E, Sweet KL, Pemmaraju N, Lane AA, Torres-Miñana L, Thompson JE, Konopleva MY, Sloss CM, Watkins K, Bedse G, Du Y, Malcolm KE, Zweidler-McKay PA, Kantarjian HM. Pivekimab sunirine (IMGN632), a novel CD123-targeting antibody-drug conjugate, in relapsed or refractory acute myeloid leukaemia: a phase 1/2 study. Lancet Oncol. 2024 Mar;25(3):388-399. doi: 10.1016/S1470-2045(23)00674-5. PMID: 38423051; PMCID: PMC11103591.
[2] Shimony S, Luskin MR, Gangat N, LeBoeuf NR, Feraco AM, Lane AA. Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): 2025 Update on Diagnosis, Pathophysiology, Risk Assessment, and Management. Am J Hematol. 2025 Aug;100(8):1408-1422. doi: 10.1002/ajh.27737. Epub 2025 Jun 17. PMID: 40525728. [Article]
[3] Pemmaraju N, Marconi G, Montesinos P, Lane AA, Mazzarella L, Sallman DA, Ulrickson ML, Schiller GJ, Erba HP, Wang ES, Walter RB, Deconinck E, Aribi A, Legrand O, Lebon D, Maisano V, Martinelli G, DeAngelo DJ, Derenzini E, Du Y, Lakshmikanthan S, Potluri J, Kantarjian HM, Daver NG. Pivekimab Sunirine in Blastic Plasmacytoid Dendritic Cell Neoplasm. J Clin Oncol. 2026 Apr;44(10):861-873. doi: 10.1200/JCO-25-02083. Epub 2026 Feb 11. PMID: 41671533; PMCID: PMC13011954. [Article]
Featured image: AbbVie Booth – ASH 2018. Photo courtesy © 2018 – 2026 Sunvalley Communication.
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