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Dr Hernandez-Ilizaliturri on Studying Immunologic Changes With Venetoclax in CLL

Francisco J. Hernandez-Ilizaliturri, MD, discusses the rationale behind assessing immunologic changes seen with venetoclax treatment in patients with CLL.

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    “Observations in the clinic led us to believe that patients with CLL have an impaired immune system, and we wanted to find a way to reverse that.”

    Francisco J. Hernandez-Ilizaliturri, MD, a professor of, oncology in the, Department of Medicine – Lymphoma, the director of, Lymphoma Research, the head of the, Lymphoma Translational Research Lab, and an associate professor in the, Department of Immunology at, Roswell Park Comprehensive Cancer Center; as well as a clinical professor in the, Department of Medicine at the, Jacobs School of Medicine and Biomedical Sciences at the, University at Buffalo, discussed, the rationale for investigating immunologic changes associated with venetoclax (Venclexta) treatment in patients with chronic lymphocytic leukemia (CLL).

    Patients with CLL frequently exhibit immune dysfunction characterized by an increased risk of secondary malignancies and recurrent infections, Hernandez-Ilizaliturri explained. These clinical observations, along with reduced responsiveness to T-cell–engaging immunotherapies such aslike CAR T-cell therapy and bispecific antibodies, highlight a broader impairment in immune surveillance and cellular immunity within this population, he stated. In response, investigators at Roswell Park initiated research efforts to evaluate how venetoclax may modulate immune function in CLL.

    The investigation’sal rationale stemmeds from the hypothesis that venetoclax, through selective inhibition of BCL-2 and reduction of leukemic burden, may alleviate immune suppression and facilitate immune reconstitution. Hernandez-Ilizaliturri noted that oOngoing analyses are focused on assessing changes in T-cell phenotype, exhaustion markers, and function before and after venetoclax treatment. Early clinical and translational data suggest that venetoclax may contribute to partial restoration of T-cell compartments, potentially enhancing the efficacy of subsequent immune-based therapies.

    Moreover, as T-cell–redirecting agents become increasingly integrated into the B-cell malignancies treatment landscape paradigmfor B-cell malignancies, understanding the underlying immune contexture in CLL is essential,. Hernandez-Ilizaliturri emphasized that patients with CLL may not respond as robustly to immunotherapies as those with other lymphoid malignancies, in part due to baseline immune dysfunction. These findings have led to a growing interest in therapeutic sequencing strategies that optimize immune responsiveness prior to the initiation of T-cell–based therapies, he concluded.


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