Dr. Shadman on the Efficacy of Venetoclax in CLL

Mazyar Shadman, MD, MPH
Published: Monday, Aug 19, 2019



Mazyar Shadman, MD, MPH, assistant member, Clinical Research Division, Fred Hutchinson Cancer Research Center, assistant professor, Medical Oncology Division, University of Washington School of Medicine, and attending physician, Hematologic Malignancies, Seattle Cancer Care Alliance, discusses the efficacy of venetoclax (Venclexta) in chronic lymphocytic leukemia (CLL).

The BCL-2 inhibitor is being tested in many hematologic malignancies. In multiple myeloma, the FDA placed a hold on all clinical trials examining the agent due to toxicity concerns. Although the hold on venetoclax has been lifted for certain trials, there is still no indication for it in the disease. The drug has also shown a lot of activity in mantle cell lymphoma (MCL) as a single agent and in combination, says Shadman.

In CLL, some high-risk patients have genetic abnormalities that make the CLL cells resistant to the normal death mechanisms in the cancer cells. Because venetoclax works by inducing apoptosis related to BCL-2—a protein that's highly expressed in CLL—high responses have been observed irrespective of risk status. The same principle applies to lymphoid malignancies, adds Shadman, specifically MCL. Venetoclax currently has an indication in CLL as well as acute myeloid leukemia, but its use may be expanded to other diseases pending further investigation.
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Mazyar Shadman, MD, MPH, assistant member, Clinical Research Division, Fred Hutchinson Cancer Research Center, assistant professor, Medical Oncology Division, University of Washington School of Medicine, and attending physician, Hematologic Malignancies, Seattle Cancer Care Alliance, discusses the efficacy of venetoclax (Venclexta) in chronic lymphocytic leukemia (CLL).

The BCL-2 inhibitor is being tested in many hematologic malignancies. In multiple myeloma, the FDA placed a hold on all clinical trials examining the agent due to toxicity concerns. Although the hold on venetoclax has been lifted for certain trials, there is still no indication for it in the disease. The drug has also shown a lot of activity in mantle cell lymphoma (MCL) as a single agent and in combination, says Shadman.

In CLL, some high-risk patients have genetic abnormalities that make the CLL cells resistant to the normal death mechanisms in the cancer cells. Because venetoclax works by inducing apoptosis related to BCL-2—a protein that's highly expressed in CLL—high responses have been observed irrespective of risk status. The same principle applies to lymphoid malignancies, adds Shadman, specifically MCL. Venetoclax currently has an indication in CLL as well as acute myeloid leukemia, but its use may be expanded to other diseases pending further investigation.



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