Dr Koff on Frontine and Maintenance Treatment Decision-Making in MCL

Jean L. Koff, MD, MS, associate professor, Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, discusses factors that influence treatment decision-making for patients with mantle cell lymphoma (MCL) in the frontline and maintenance settings.

In the context of newly diagnosed MCL, treatment decisions are primarily driven by assessing a patient’s eligibility for autologous stem cell transplant (ASCT) and determining the appropriate induction regimen, Koff begins. Historically, ASCT has been a standard approach, but its role in MCL is currently evolving, she says. Patients are stratified based on their ability to tolerate aggressive induction regimens or their need for less intensive options, she notes.

The selection of BTK inhibitors in the frontline and maintenance settings has been guided by data from the phase 2 TRIANGLE trial (NCT02858258), which evaluated ibrutinib (Imbruvica) as part of a chemoimmunotherapy regimen and as single-agent maintenance therapy, with or without ASCT, Koff states. However, data now indicate that newer covalent BTK inhibitors, such as acalabrutinib (Calquence) and zanubrutinib (Brukinsa), generate efficacy profiles that are comparable with that of ibrutinib but offer improved tolerability, according to Koff. In 2017, acalabrutinib was approved for the treatment of adult patients with MCL who have received at least 1 prior therapy. In 2019, zanubrutinib was also approved for this indication. Data with acalabrutinib and zanubrutinib have shifted clinical practice in favor of utilizing these newer agents over ibrutinib for the management of various lymphoma subtypes, including MCL.

Although the TRIANGLE trial supported the use of ibrutinib in the MCL treatment paradigm, the National Comprehensive Cancer Network guidelines for the management of MCL now provide a category 2B recommendation to consider substituting newer-generation BTK inhibitors for ibrutinib, Koff explains. This change underscores a trend toward individualized treatment plans based on tolerability and patient-specific factors, rather than strictly adhering to historical data with ibrutinib-based regimens, Koff concludes.