Future Directions in the Research of Acalabrutinib in MCL
Prof Martin Dreyling discusses the unmet needs in MCL and the potential next lines of research on the BTK inhibitor acalabrutinib.
The EU approval of acalabrutinib (Calquence) plus bendamustine and rituximab (BR) for the first-line treatment of mantle cell lymphoma (MCL) provides a much-needed option for physicians and, most importantly, patients. Here, Prof Martin Dreyling, professor in the Department of Medicine in the University Hospital and head of the lymphoma program at the Department of Medicine III, LMU Hospital Munich, discusses the benefits of this approval, as well as the unmet needs that still exist in the field.
According to Dreyling, a major positive is the improvement in first-line treatment, where the potential for patient benefit is greatest. In this setting, extending progression-free survival by 50% translates to years, significantly improving a patient's outlook. This is a far more impactful gain than the mere months seen in relapsed disease. For the majority of patients, especially older individuals, we now have a genuinely more effective treatment.
However, a personal reservation for Dreyling, based on study-to-study comparisons, is that bendamustine may not be the ideal combination partner due to its strong immunosuppressive side effects. Other chemotherapy combinations appear to offer superior benefits.
"If you see other studies with other chemotherapy combination partners, the benefit seems to be superior. For the routine application, to be honest, if I were to treat a new patient with this regimen tomorrow, my first consideration would be to reduce or adapt the bendamustine dose, either by reducing the number of cycles or the cumulative dose per cycle," said Dreyling in the interview.
Looking ahead, the crucial question is whether a chemotherapy backbone is truly needed at all, or if it can be substituted with a purely targeted combination. Several randomized studies are currently investigating these nonchemotherapy approaches, which is particularly important for older patients where tolerability is a significant concern.
