An emerging hope for patients battling blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare and aggressive cancer of the blood, has been uncovered in a recent international Phase I/II clinical trial investigating the antibody-drug conjugate pivekimab sunirine (PVEK). BPDCN notoriously challenges clinicians due to its hybrid biological nature, straddling both lymphoid and myeloid malignancies, complicating diagnosis and treatment strategies. This trial, spearheaded by researchers at The University of Texas MD Anderson Cancer Center, unveiled encouraging data pointing toward a potentially paradigm-shifting therapeutic option.
BPDCN cells uniquely overexpress the CD123 antigen on their surface, a molecular characteristic that has provided a viable target for novel treatments. PVEK, a next-generation antibody-drug conjugate, precisely exploits this feature. By tethering a potent cytotoxic drug to an antibody that specifically binds CD123, PVEK delivers the lethal payload directly into cancer cells. This targeted approach aims to maximize tumor cell death while sparing healthy tissue, thus enhancing both efficacy and safety profiles compared to conventional chemotherapeutics.
The multicenter CADENZA trial enrolled 84 patients diagnosed with BPDCN, split between frontline treatment naive individuals and those with relapsed or refractory disease. Of particular note, the frontline cohort comprised 33 patients, many presenting with highly complex clinical pictures due to prior or simultaneous malignancies. Treatment with PVEK as a monotherapy yielded an impressive overall response rate of 85% in this group, with a remarkable 75% achieving complete remission. These response rates are unprecedented in BPDCN, a malignancy historically marked by dismal outcomes and limited therapeutic advances.
Median overall survival for patients receiving frontline PVEK reached 16.6 months, a significant extension in a disease where survival is typically measured in mere months without successful stem cell transplantation. Encouragingly, eight patients from the frontline group managed to proceed to hematopoietic stem cell transplantation (HSCT), which remains the only curative modality for BPDCN to date. Facilitating transplant eligibility through effective induction therapy could profoundly improve long-term survival and alter the disease’s lethal trajectory.
In the cohort with relapsed or refractory BPDCN, PVEK monotherapy demonstrated activity with a lower overall response rate of 35%, yet still prolonged median overall survival to 5.8 months. While this subset represents a particularly treatment-resistant population, the partial responses observed underscore PVEK’s potential utility beyond first-line use. Treatment-related side effects were generally manageable, with peripheral edema and infusion-related reactions constituting the most common adverse events, supporting PVEK’s favorable tolerability.
This trial builds upon earlier clinical advances in CD123-directed therapies. Tagraxofusp-erzs, an FDA-approved agent targeting the same antigen, has been the cornerstone of BPDCN treatment but with significant limitations and toxicities. The development of PVEK offers a next-generation approach by coupling refined antibody specificity with a more potent cytotoxic payload, potentially overcoming resistance mechanisms that hamper current options.
BPDCN’s clinical complexity arises from its involvement of multiple organ systems, including skin lesions, bone marrow infiltration, and lymphadenopathy, frequently confounding diagnosis. The disease’s overlapping features with other hematologic malignancies often delay effective treatment initiation. The precise targeting of CD123 by PVEK represents a major advancement by exploiting a defining molecular marker of BPDCN cells, ushering in a more tailored and effective therapy.
Beyond BPDCN, researchers at MD Anderson are extending investigations of PVEK into acute myeloid leukemia (AML), another aggressive myeloid malignancy where CD123 expression is prevalent. Preliminary results from combination regimens incorporating PVEK indicate promising efficacy, signaling potential broader applications for this therapeutic platform. These investigations may inaugurate a new era of CD123-targeted therapies across multiple hematologic cancers.
The results of the CADENZA trial were recently published in the Journal of Clinical Oncology, further validating the scientific rigor and clinical relevance of these findings. The study was led by Naveen Pemmaraju, MD, and Naval Daver, MD, both professors of Leukemia at MD Anderson. Their leadership underscores the pivotal role of academic research centers in bringing innovative treatments from bench to bedside.
This research was supported by AbbVie, reflecting the critical partnership between academia and industry in accelerating drug development for rare cancers. As PVEK continues through clinical development pipelines, the accumulating data support its consideration as a new frontline standard of care for BPDCN. Such advances not only kindle hope for patients with this devastating diagnosis but also exemplify the extraordinary potential of antibody-drug conjugates in oncology.
In sum, the CADENZA trial offers compelling evidence that pivekimab sunirine is reshaping the therapeutic landscape for BPDCN. By harnessing precise molecular targeting combined with potent cytotoxicity, PVEK achieves high and durable response rates, extending survival and expanding curative options via stem cell transplantation. This breakthrough heralds a novel chapter in the management of rare hematologic malignancies and augurs improved outcomes for patients who desperately need new treatment avenues.
Subject of Research: Clinical evaluation of pivekimab sunirine (PVEK) in blastic plasmacytoid dendritic cell neoplasm (BPDCN)
Article Title: Phase I/II CADENZA Trial Reveals Pivekimab Sunirine as a Promising Therapeutic in BPDCN
News Publication Date: 2025
Web References:
Journal of Clinical Oncology: https://ascopubs.org/doi/10.1200/JCO-25-02083
MD Anderson Cancer Center: https://www.mdanderson.org/
FDA approval of tagraxofusp-erzs: https://www.fda.gov/drugs/fda-approves-tagraxofusp-erzs-blastic-plasmacytoid-dendritic-cell-neoplasm
References:
Pemmaraju N, Daver N, et al. “Efficacy of Pivekimab Sunirine in Blastic Plasmacytoid Dendritic Cell Neoplasm: Results from the CADENZA Trial.” Journal of Clinical Oncology, 2025.
Keywords:
Blastic plasmacytoid dendritic cell neoplasm, BPDCN, pivekimab sunirine, antibody-drug conjugate, CD123, hematologic malignancy, stem cell transplant, acute myeloid leukemia, targeted therapy, rare blood cancer, clinical trial, MD Anderson Cancer Center
Tags: antibody-drug conjugate therapyblastic plasmacytoid dendritic cell neoplasm treatmentCD123 antigen targetingcomplex clinical management of rare cancerscytotoxic drug delivery systemsefficacy and safety of PVEKfrontline therapy for BPDCNhematologic cancer researchinnovative oncology treatmentsMD Anderson Cancer Center researchnovel cancer therapiesPhase I/II clinical trial results
