Dr. Owen on Choosing Between BTK Inhibitors in CLL

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Carolyn Owen, MD, FRCPC, associate professor, medicine and oncology, Arnie Charbonneau Cancer Institute, discusses factors to consider when deciding whether to use the BTK inhibitors ibrutinib (Imbruvica), acalabrutinib (Calquence), or zanubrutinib (Brukinsa) in patients with chronic lymphocytic leukemia (CLL).

Decisions regarding which covalent BTK inhibitor to use to treat patients with CLL are often influenced by funding implications in different regions of the world, Owen says. In the United States, the available BTK inhibitor options in the frontline and relapsed/refractory CLL settings are ibrutinib, acalabrutinib, and zanubrutinib. In Canada, ibrutinib and acalabrutinib are available for previously untreated patients with CLL and those with relapsed or refractory CLL.

In Alberta, Canada, acalabrutinib and ibrutinib receive similar funding and have the same indications in CLL, making them both available options to choose between, Owen explains. Although zanubrutinib is not approved by Health Canada and therefore not commercially available, patients with CLL can receive it through a compassionate access program, Owen notes.

Compared with acalabrutinib and zanubrutinib, ibrutinib is a less-favored covalent BTK inhibitor in the frontline CLL setting because of its toxicity profile, Owen emphasizes. Findings in relapsed/refractory CLL from the phase 3 ELEVATE-RR trial (NCT02477696), which compared acalabrutinib with ibrutinib, and the phase 3 ALPINE trial (NCT03734016), which compared zanubrutinib with ibrutinib, have shown that the second-generation BTK inhibitors acalabrutinib and zanubrutinib do not have inferior efficacy compared with ibrutinib and demonstrate favorable safety profiles in many patients with CLL, Owen says.

Choices between acalabrutinib and zanubrutinib in CLL may be affected by how familiar physicians are with each agent, which often correlates with how long the therapies have been available for their use, Owen notes. As acalabrutinib has been available for a longer period of time and has produced positive results in patients, this agent remains a reliable treatment option, Owen says. However, zanubrutinib can be considered in patients who are intolerant to acalabrutinib or who would prefer the once-daily dosing schedule available with zanubrutinib instead of the twice-daily dosing schedule with acalabrutinib, Owen concludes.