Monica D. Mead, MD, discusses reasons for the declining use of the BTK inhibitor ibrutinib in patients with mantle cell lymphoma.
Monica D. Mead, MD, assistant clinical professor, medicine, Hematologic Malignancy, the University of California, Los Angeles (UCLA), UCLA Health, UCLA Jonsson Comprehensive Cancer Center, discusses reasons for the declining use of the BTK inhibitor ibrutinib (Imbruvica) in patients with mantle cell lymphoma (MCL).
As ibrutinib was the first BTK inhibitor to gain FDA approval for patients with MCL, it was once the only BTK inhibitor in use in this population, Mead says. In 2013, the FDA granted accelerated approval to ibrutinib for patients with MCL who had received at least 1 prior therapy. This approval was supported by findings from a single-arm phase 2 trial (NCT01236391), in which 68% of patients responded with ibrutinib.
However, ibrutinib use declined with the FDA approvals of 2 second-generation BTK inhibitors, acalabrutinib (Calquence) and zanubrutinib (Brukinsa). In 2017, acalabrutinib gained accelerated FDA approval for patients with MCL who have received at least 1 prior therapy. This regulatory decision was supported by findings from the phase 2 ACE-LY-004 trial (NCT02213926), in which 81% (95% CI, 73%-87%) of patients who received acalabrutinib achieved an objective response.
Additionally, in 2019, the FDA granted accelerated approval to zanubrutinib for patients with MCL who have received 1 or more prior therapies. This approval was backed by findings from 2 single-arm trials. In both the phase 1 BGB-3111-206 trial (NCT03206970) and the phase 1/2 BGB-3111-AU-003 trial (NCT02343120), zanubrutinib elicited an objective response rate of 84% (95% CI, 74%-91%).
The declining use of ibrutinib in patients with MCL was motivated by the agent’s more severe toxicity profile when compared with acalabrutinib or zanubrutinib rather than inferior efficacy, Mead explains. Although trials comparing ibrutinib with zanubrutinib and acalabrutinib in patients with chronic lymphocytic leukemia (CLL) revealed that the 3 agents have similar efficacy profiles, ibrutinib was associated with more substantial adverse effects. Thus, the National Comprehensive Cancer Network removed ibrutinib from its list of preferred regimens for patients with CLL. Moreover, on April 6, 2023, AbbVie voluntarily withdrew the FDA indication for ibrutinib in patients with pretreated MCL based on safety findings from the confirmatory phase 3 SHINE (NCT01776840) and SELENE (NCT01974440) trials.