ASH 2025: New data highlights promise of pivekimab sunirine in two aggressive blood cancers ​

(Press-News.org) Two clinical studies demonstrate high response rates by patients with two hard-to-treat and aggressive blood cancers  

Pivekimab sunirine (PVEK) targets the CD123 antigen, which is overexpressed in both diseases 

Frontline triplet regimen including PVEK shows promise for hard-to-treat AML in patients who are not eligible for intensive chemotherapy 

PVEK monotherapy demonstrates strong responses, enables stem cell transplant for high-risk subgroup of BPDCN patients  

ORLANDO, DECEMBER 8, 2025 – Researchers from The University of Texas MD Anderson Cancer Center presented promising new data from two ongoing studies of pivekimab sunirine (PVEK), an antibody-drug conjugate targeting CD123, in treating two aggressive blood cancers at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition.  

In a Phase Ib/II trial led by Naval Daver, M.D., professor of Leukemia, patients with newly diagnosed CD123-positive acute myeloid leukemia (AML) who were unable to undergo intensive chemotherapy had strong response rates from the triplet combination of venetoclax (VEN), azacitidine (AZA) and PVEK. Daver presented findings Dec. 7 (Abstract 651). 

In the Phase I/II registrational CADENZA study led by Naveen Pemmaraju, M.D., professor of Leukemia, PVEK monotherapy achieved high response rates in a subgroup of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) – a rare and aggressive blood cancer – and other blood cancers. Pemmaraju presented the findings Dec. 8 (Abstract 5195). 

All ASH content from MD Anderson can be found at MDAnderson.org/ASH. 

How did PVEK benefit patients with CD123-positive AML? 

In previous study led by MD Anderson, the combination of VEN and AZA improved survival over AZA alone for patients with newly diagnosed CD123-positive AML who were not eligible for intensive chemotherapy. However, there is room to further improve outcomes in this population. Therefore, this study explored the addition of PVEK to the established backbone of VEN and AZA given that CD123 is overexpressed on certain leukemia cells. 

Forty-nine older chemotherapy-ineligible patients with CD123-positive AML received the triplet regimen. At median follow-up of 10 months, 63.3% of patients achieved complete remission (CR), 79.6% achieved CR including incomplete hematologic recovery, and 73.5% achieved CR including partial hematologic recovery.  

Most patients also showed no measurable residual disease (MRD) by more sensitive testing. Eight patients were able to bridge to stem cell transplant. The treatment was generally well-tolerated, and no new major side effects were observed. The findings suggest the triplet regimen is a safe and potentially effective option for patients with this difficult-to-treat AML. 

“This triplet regimen may represent a significant step forward for older patients with CD123-positive AML who are not candidates for intensive chemotherapy,” Daver said. “The remission and MRD rates we observed are very encouraging and support further development in larger trials.” 

How did patients with BPDCN benefit from PVEK in the CADENZA study?  
Blastic plasmacytoid dendritic cell neoplasm is a rare, aggressive blood cancer that affects a patient’s skin, bone marrow, and lymph nodes, and there is an unmet need for improved frontline therapies. Because CD123 is overexpressed in this cancer, the CADENZA study evaluated PVEK as a monotherapy for these patients. 

Earlier results showed promising outcomes, with 70% of newly diagnosed BPDCN patients achieving complete or near-complete remission. However, a high-risk subgroup of approximately 20% of BPDCN patients also have other blood cancers, diagnosed either before or at the same time as the BPDCN, making their treatment more complex and challenging. Yet these patients also responded well to PVEK therapy. 

“We identified a major breakthrough for the subgroup of patients who are not only dealing with BPDCN but also other blood cancers, leaving them historically with fewer treatment options,” Pemmaraju said. “These results suggest that PVEK treatment may be just as effective even in this high-risk subgroup, which is important progress for these patients.”  

In this important sub-group of patients, PVEK monotherapy demonstrated an overall response rate of 90.9%. The median survival was approximately 17 months, and nearly half were able to proceed to stem cell transplants, marking a significant milestone for this high-risk group. Side effects were overall manageable and consistent with those seen in other cancer treatments. These findings suggest that PVEK could offer a valuable new option for patients with difficult-to-treat BPDCN.  

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Both studies were supported by AbbVie. A full list of collaborating authors and their disclosures for the AML study can be found with the abstract. A full list of collaborating authors and their disclosures for the CADENZA study can be found with the abstract.  

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