Dr Mead on the Shifting Role of Ibrutinib in the Treatment of MCL

Monica D. Mead, MD, assistant clinical professor of medicine, Department of Hematologic Malignancy, the University of California, Los Angeles (UCLA), UCLA Health, UCLA Jonsson Comprehensive Cancer Center, discusses the impact of key data on the role of ibrutinib (Imbruvica) in the treatment of mantle cell lymphoma (MCL).

The FDA approvals of acalabrutinib (Calquence) in 2017 and zanubrutinib (Brukinsa) in 2019 have led to a decrease in the use of ibrutinib in both clinical trials and in practice, Mead begins. Despite this, ibrutinib remains the most studied BTK inhibitor in the frontline setting, Mead says. Currently, there are 2 randomized, phase 3 trials investigating the use of first-line ibrutinib for patients with MCL: the TRIANGLE trial (NCT02858258) and SHINE trial (NCT01776840), Mead states.

In the TRIANGLE study, treatment-naïve patients with MCL were randomly assigned to 3 different treatment arms: ibrutinib plus induction chemotherapy and autologous stem cell transplant (ASCT); ibrutinib plus induction chemotherapy without ASCT; and induction chemotherapy and ASCT alone, Mead explains. Patients in both experimental arms received 2 years of ibrutinib maintenance therapy following treatment. Results showed that adding ibrutinib to conventional therapy improved failure-free survival (FFS) rates vs ASCT alone but did not produce a superior FFS rate vs ibrutinib alone. Ibrutinib alone was also associated with a more favorable safety profile.

The SHINE trial was designed to confirm the efficacy of ibrutinib in combination with bendamustine (Avastin) and rituximab (Rituxan), followed by rituximab maintenance, for elderly patients with MCL in the treatment-naïve setting, Mead details. This trial did not meet its primary end point of improved progression-free survival, and it resulted in a higher rate of adverse effects (AEs).

Supported by data from the confirmatory SHINE trial, the FDA voluntarily withdrew their indication for ibrutinib in MCL, based on FDA requirements related to accelerated approval status.

The decision to utilize ibrutinib in clinical practice continues to be a topic of substantial debate, with many oncologists opting to substitute acalabrutinib or zanubrutinib for ibrutinib in combination with chemotherapy for older, frailer patients or younger, more intensive induction–eligible patients, Mead concludes.