Dr Gordon on Shifts in the R/R MCL Treatment Paradigm

Leo I. Gordon, MD, Abby and John Friend Professor of Oncology Research, professor, medicine (hematology and oncology), Feinberg School of Medicine, Robert H. Lurie Cancer Center, discusses the evolution of the relapsed/refractory mantle cell lymphoma (MCL) treatment paradigm.

Patients with MCL are traditionally treated with combination chemotherapy, Gordon begins. The regimen issometimes followed by autologous stem cell transplant (ASCT) as consolidation, though this approach has become less common due to recent data, Gordon begins.

However, there has been a significant shift in the first- and second-line treatment paradigms in MCL, he says. Oral BTK inhibitors, which are often combined with BCL-2 inhibitors such as venetoclax (Venclexta), are now commonly used, Gordon explains. Despite these advances, many patients still face high relapse rates, and treatment options remain limited once relapse occurs, Gordon notes.

Since the mid-2010s, a number of studies have explored novel treatments for MCL, diffuse large B-cell lymphoma (DLBCL) and, to a lesser extent, follicular lymphoma, he continues. These studies built on the foundation of allogeneic stem cell transplantation, which demonstrated improved outcomes, but higher toxicity, compared with ASCT, he reports. The donor T cells in allogeneic transplants effectively target the lymphoma but also attack normal cells and organs, leading to graft-versus-host disease (GVHD), Gordon says.

One of the major goals of cellular therapy research has been to replicate the beneficial effects of donor T cells attacking the tumor without the harmful effects on normal tissue, he expands. Research has been conducted to develop new approaches that modify a patient’s own T cells to attack the tumor while minimizing toxicity, Gordon explains. This innovative therapy, known as CAR T-cell therapy, represents a more focused and strategic version of what allogeneic stem cell transplants aim to achieve without the complications of GVHD, he concludes.