Bcl-2 Inhibition With ABT-199 in CLL, Lymphomas

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ABT-199 is an orally bioavailable selective inhibitor of the Bcl-2 protein, which is commonly overexpressed in a variety of lymphoid malignancies, notes Brad S. Kahl, MD. The agent is a BH3 mimetic, which improves efficacy while lowering the thrombocytopenia seen with previous Bcl-2 inhibitors. In early phase I findings, single-agent ABT-199 induced an overall response rate of near 85% in chemotherapy refractory patients with bulky chronic lymphocytic leukemia. Given the different mechanisms of action, the combination of the BTK inhibitor ibrutinib and ABT-199 could be a dynamic combination, Kahl believes.

High-grade B-cell lymphomas with dual chromosomal rearrangements, or double hit lymphomas, remain challenging to treat, Kahl notes. In general, this population has a rearrangement in both MYC and Bcl-2. To address this unmet need, trials are looking at the combination of ABT-199 with R-CHOP for patients with large cell lymphoma, Kahl states.