Researchers presented new data from two ongoing studies of pivekimab sunirine, an antibody-drug conjugate targeting CD123, in treating two aggressive blood cancers at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition.
In a phase Ib/II trial led by Naval Daver, MD, Professor of Leukemia at The University of Texas MD Anderson Cancer Center, 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, azacitidine, and pivekimab sunirine (Abstract 651).
In the phase I/II registrational CADENZA study led by Naveen Pemmaraju, MD, also Professor of Leukemia at MD Anderson, pivekimab sunirine monotherapy achieved high response rates in a subgroup of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) and other hematologic malignancies (Abstract 5195).
Use in a Triplet for AML
In a previous study, the combination of venetoclax and azacitidine improved survival over azacitidine 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, the phase Ib/II study presented at ASH 2025 explored the addition of pivekimab sunirine to the established backbone of venetoclax and azacitidine given that CD123 is overexpressed on certain leukemia cells.
Forty-nine older chemotherapy-ineligible patients with CD123-positive AML received the triplet regimen. At a median follow-up of 10 months, 63.3% of patients achieved complete remission, 79.6% achieved complete response including incomplete hematologic recovery, and 73.5% achieved complete response 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,” Dr. Daver said. “The remission and MRD rates we observed are very encouraging and support further development in larger trials.”
CADENZA: Pivekimab Sunirine as Monotherapy
BPDCN 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 for this malignancy. Because CD123 is overexpressed in this cancer, the CADENZA study evaluated pivekimab sunirine 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 pivekimab sunirine 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,” Dr. Pemmaraju said. “These results suggest that [pivekimab sunirine] treatment may be just as effective even in this high-risk subgroup, which is important progress for these patients.”
In this important subgroup of patients, pivekimab sunirine 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 pivekimab sunirine could offer a valuable new option for patients with difficult-to-treat BPDCN.
Disclosure: Both studies were supported by AbbVie.
