New BTK Agents and Combinations Are on the Horizon for B-cell Malignancies

Christina T. Loguidice
Published: Thursday, Dec 05, 2019
Ian W. Flinn, MD, PhD, director, Blood Cancer Research Program, Sarah Cannon Research Institute

Ian W. Flinn, MD, PhD

The bruton tyrosine kinase (BTK) plays a key role in B-cell receptor signaling, regulating cellular proliferation and survival in patients with B-cell malignancies.1 In 2013, the FDA approved the first BTK inhibitor, ibrutinib (Imbruvica), which has since redefined the standard of care for many B-cell malignancies; however, its off-target activities on non-BTK kinases limits its use in certain populations.1,2 Now the field is packed with novel agents and combinations that are setting the stage for further advancements.

During a recent OncLive Peer Exchange®, a panel of leukemia and lymphoma experts discussed 2 emerging BTK inhibitors: acalabrutinib (Calquence), which was approved in October 2017 for previously treated mantle cell lymphoma (MCL) and received a breakthrough therapy designation in August 2019 for chronic lymphocytic leukemia (CLL), and zanubrutinib (Brukinsa), which was approved in November for patients with MCL who have received at least 1 prior therapy.3-5

The panelists examined key studies assessing these second-generation BTK inhibitors as a treatment for CLL, MCL, and Waldenström macroglobulinemia (WM). They also discussed the promise of new and emerging BTK combinations, including ibrutinib/venetoclax (Venclexta) in patients with CLL.

Studies assessing BTK inhibitor combinations are adding to the evidence that positive synergistic effects occur when BTK inhibitors are correctly combined with other active agents, which may be particularly important for certain patient subsets, including older adults and high-risk patients. “I think this is a very exciting time in B-cell malignancies. We have a lot of new tools available to us. Most agents were developed as single agents, but I think combinations are particularly exciting,” Matthew S. Davids, MD, MMSc, said.

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