Dr. Ma on First- and Second-Generation BTK Inhibitors in B-Cell Malignancies

Shuo Ma, MD, PhD, associate professor of medicine (hematology and oncology), Robert H. Lurie Comprehensive Cancer Center, ​Northwestern University Feinberg School of Medicine, highlights ongoing ​research with BTK inhibitor​s in B​-cell malignancies. 

Currently, the BTK inhibitors ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa) ​have indications in chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström macroglobulinemia, ​says Ma. Ibrutinib is a first-generation BTK inhibitor, whereas acalabrutinib and zanubrutinib are second-generation ​BTK inhibitors.

Ibrutinib​ inhibits the BTK enzyme, which is a critical component of B​-cell biology, survival, and proliferation. However, ibrutinib affects other tyrosine kinases, such as EGFR​, Ma explains.

As a result, patients may experience off-target toxicities with ibrutinib, ​adds Ma.

​Although head-to-head clinical trials are needed, acalabrutinib and zanubrutinib may elicit less toxicity compared with ibrutinib as the agents are more selective, Ma concludes.