Dr Burke on the Influence of the SHINE and TRIANGLE Trials on Ibrutinib Use in MCL

John M. Burke, MD, associate chair of the Hematology Research Program for US Oncology and a medical oncologist and hematologist at Rocky Mountain Cancer Centers, discusses the influence of two key BTK inhibitor combination studies on therapeutic approaches for patients with previously untreated mantle cell lymphoma (MCL).

Both the phase 3 SHINE (NCT01776840) and TRIANGLE (NCT02858258) studies have greatly influenced the role of ibrutinib (Imbruvica) in the treatment of patients with MCL in the frontline setting, Burke begins.

In 2013, ibrutinib gained accelerated approval for the treatment of patients with MCL who received at least one prior line of therapy based on efficacy data from an open-label, multicenter, single-arm phase 2 study (NCT01236391).

The confirmatory SHINE trial was conducted to confirm the benefit of ibrutinib plus bendamustine and rituximab (Rituxan) with rituximab maintenance for elderly patients with MCL. Although the study did meet its primary end point of improved progression-free survival vs bendamustine and rituximab alone, it resulted in a higher rate of adverse effects (AEs).

The TRIANGLE study evaluated the addition of ibrutinib to induction chemotherapy with or without autologous stem cell transplant (ASCT) followed by ibrutinib maintenance in this population. Similarly, the ibrutinib plus ASCT regimen produced a greater failure-free survival (FFS) rate than ASCT alone, Burke reports. However, ASCT plus ibrutinib did not produce a superior FFS rate vs ibrutinib alone.

These studies demonstrated that adding ibrutinib to conventional therapy improved survival outcomes for transplant eligible or ineligible patients and allowed them to remain in remission for a longer period of time, Burke states. Despite these findings, the indication for ibrutinib in MCL was voluntarily withdrawn according to FDA requirements related to accelerated approval status.* The agent's indication for marginal zone lymphoma was also withdrawn according to findings from the phase 3 SELENE study (NCT01974440).

This decision has complicated the selection of ibrutinib in clinical practice and has led to substantial debate about where the agent should be utilized, Burke states. However, ibrutinib-containing regimens remain of interest in MCL, and investigations of this and other BTK inhibitors are ongoing.