Dr Islam on Updated Safety and Efficacy Data With FDA-Approved BTK Inhibitors in CLL

Prioty Islam, MD, MSc, attending physician, medical oncologist, Leukemia, Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, discusses the impact of the updated safety and efficacy data seen with FDA-approved BTK inhibitors in patients with chronic lymphocytic leukemia (CLL).

BTK inhibitors are approved across all treatment lines in CLL, Islam begins. As such, these agents can be used in both the frontline and relapsed/refractory settings, Islam explains. Therefore, if a BTK inhibitor is being used in the relapsedsetting, it typically means that the patient’s disease progressed on a frontline treatment, such as venetoclax (Venclexta), Islam explains.

Currently, there are 3 covalent BTK inhibitors available for use in CLL–ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa). The most recent BTK inhibitor to be approved was zanubrutinib, which received its designation in January 2023 for patients with CLL or small lymphocytic lymphoma (SLL) based on data from the phase 3 ALPINE (NCT03734016) and SEQUOIA trials (NCT03336333). Overall, there are now many different treatment options to offer patients with CLL, Islam emphasizes.

However, acalabrutinib and zanubrutinib have become preferred BTK inhibitors due to improved safety data, as well as improved efficacy data, specifically with zanubrutinib, in the relapsed setting, Islam continues.

In the phase 3 ELEVATE-RR trial (NCT02477696), acalabrutinib met the noninferiority end point of the study vs ibrutinib, whereas in the phase 3 ALPINE trial (NCT03734016) zanubrutinib demonstrated superiority over ibrutinib. For patients who have been on ibrutinib and are responding, it may be beneficial to raise the conversation of switching the patient over to either acalabrutinib or zanubrutinib due to concerns over long-term safety with the first-generation BTK inhibitor. Overall, these are 3 efficacious agents available for patients in all lines, making this an optimaltime to be using BTK inhibitors in CLL, Islam concludes.

Clinicians referring a patient to MSK can do so by visiting msk.org/refer, emailing referapatient@mskcc.org, or by calling 833-315-2722.