Dr Kahl on the Rationale for Adding Bortezomib to BR Induction in MCL

"We knew that for younger patients who could handle intense treatments, the best strategy was some semi-intensive induction followed by hematopoietic stem cell transplantation. Our older patients weren’t candidates for that kind of strategy. Therefore, we decided to design a study for older patients with MCL, in which we would test the addition of bortezomib to BR induction…"

Brad S. Kahl, MD, a professor in the John T. Milliken Department of Oncology in the Division of Oncology at the Washington University School of Medicine, discussed the rationale for evaluating the addition of bortezomib (Velcade) to bendamustine/rituximab (Rituxan; BR) induction therapy with rituximab with or without lenalidomide (Revlimid) maintenance for patients with mantle cell lymphoma (MCL).

An open-label, randomized, phase 2 trial (NCT01415752) enrolled older patients with MCL across 4 treatment arms: BR followed by rituximab maintenance; BR plus bortezomib followed by rituximab maintenance; BR followed by rituximab and lenalidomide maintenance; and BR plus bortezomib followed by rituximab and lenalidomide maintenance. The trial aimed to identify strategies that could improve remission duration and long-term outcomes in patients who were not candidates for intensive therapies, such as autologous hematopoietic stem cell transplantation.

The study was designed in 2011, a period when BR had emerged as a well-tolerated and effective induction option for older patients, Kahl explained. Maintenance rituximab had also demonstrated potential to prolong responses in this population, which supported its use as a control backbone, he added. Since both bortezomib and lenalidomide were FDA approved for relapsed/refractory MCL at the time, their incorporation into frontline treatment warranted investigation, Kahl noted.

In the absence of curative options for older adults with MCL, evaluating novel agents in the induction and maintenance settings was viewed as a critical step toward improving long-term outcomes, Kahl stated. The combination approach was developed to assess whether outcomes could be enhanced by introducing targeted agents earlier in the treatment paradigm, he said. These regimens were selected to balance potential efficacy with tolerability in a population often excluded from transplant-based strategies, Kahl concluded.