Two ongoing studies show that pivekimab sunirin shows promise in treating aggressive blood cancers

Two ongoing studies show that pivekimab sunirin shows promise in treating aggressive blood cancers

Researchers at the University of Texas MD Anderson Cancer Center presented promising new data from two ongoing studies of pivekimab sunirin (PVEK), an antibody-drug conjugate targeting CD123, in the treatment of two aggressive blood cancers, at the 67th Annual Meeting and Exhibition of the American Society of Hematology (ASH).

In a Phase Ib/II trial led by Naval Daver, MD, professor of leukemia, patients with newly diagnosed CD123-positive acute myeloid leukemia (AML) who were unable to undergo intensive chemotherapy demonstrated strong response rates to the triplet combination of venetoclax (VEN), azacitidine (AZA), and PVEK. Daver presented his results on December 7 (Abstract 651).

In the pivotal Phase I/II CADENZA trial led by Naveen Pemmaraju, MD, professor of leukemia, PVEK monotherapy achieved high response rates in a subset of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare and aggressive blood cancer, and other blood cancers. Pemmaraju presented the results on December 8 (Abstract 5195).

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

What benefit did PVEK have for patients with CD123-positive AML?

In a previous study led by MD Anderson, the combination of VEN and AZA improved survival over AZA alone in patients with newly diagnosed CD123-positive AML who were ineligible for intensive chemotherapy. However, there is room for further improvement in outcomes in this population. Therefore, this study examined the addition of PVEK to the established backbone of VEN and AZA given that CD123 is overexpressed on certain leukemia cells.

Forty-nine elderly patients with CD123-positive AML who were ineligible for chemotherapy received the triplet regimen. At the median follow-up of 10 months, 63.3% of patients achieved complete response (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) on more sensitive tests. Eight patients were able to undergo a stem cell transplant. Treatment was generally well tolerated and no new serious adverse events were observed. The results suggest that triplet therapy is a safe and potentially effective option for patients with this difficult-to-treat AML.

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

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 first-line therapies. Because CD123 is overexpressed in this cancer, PVEK was evaluated as monotherapy for these patients in the CADENZA trial.

Previous results showed promising results: 70% of newly diagnosed BPDCN patients achieved complete or near-complete remission. However, a high-risk subgroup of approximately 20% of BPDCN patients also suffer from other blood cancers that are diagnosed either before or concurrently with BPDCN, making their treatment more complex and challenging. But these patients also responded well to PVEK therapy.

We have seen a major breakthrough for the subset of patients who have not only BPDCN but also other blood cancers, leaving them with fewer treatment options in the past. These results suggest that PVEK treatment may be just as effective even in this high-risk subgroup, representing an important advance for these patients.”

Naveen Pemmaraju, MD, professor of leukemia

In this important subgroup of patients, PVEK monotherapy demonstrated an overall response rate of 90.9%. Median survival was approximately 17 months, and nearly half were able to proceed with stem cell transplantation, representing a significant milestone for this high-risk group. Overall, side effects were manageable and consistent with those seen with other cancer treatments. These results suggest that PVEK may provide a valuable new option for patients with difficult-to-treat BPDCN.

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