Dr Dreyling on the Rationale for Adding Acalabrutinib to BR in High-Risk MCL

"In patients [approximately 70 years of age, there are typically] some age-related comorbidities, and we can’t use such an intensified approach. In these patients, the standard of care [SOC] is BR, mostly based on tolerability. Therefore, the control arm [of the ECHO trial] was BR plus rituximab maintenance."

Martin Dreyling, MD, full professor, Department of Medicine, University Hospital LMU Munich, discussed the rationale for adding acalabrutinib (Calquence) to bendamustine plus rituximab (Rituxan; BR) for patients with previously untreated, high-risk mantle cell lymphoma (MCL) in the phase 3 ECHO trial (NCT02972840).

The development of this trial was necessitated by the demographic reality of the disease; patients with MCL typically have a median age of approximately 70 years. Although treatment strategies for younger patients have traditionally involved efforts toward dose intensification—a strategy proven effective in trials like the phase 3 TRIANGLE (NCT02858258), which showed significant benefit by adding a BTK inhibitor to intense chemotherapy. This approach is generally not feasible for the majority of patients with MCL.

Due to the presence of age-related comorbidities common in patients around 70 years old, they cannot tolerate such intensified approaches. Therefore, the standard of care (SOC) for this older patient population has been BR, which is primarily favored for its improved tolerability.

The control arm of the ECHO trial was designed around this SOC, consisting of BR plus rituximab maintenance. This was compared against the addition of acalabrutinib, which is a second-generation BTK inhibitor. The key goal of the ECHO trial was to determine if adding acalabrutinib would make a difference in terms of efficacy. Dreyling noted that the regimens are comparable concerning tolerability, but acalabrutinib is specifically better tolerated than other similar options. This improved tolerability is vital, especially considering the adverse effects associated with the treatment of older patients, such as bleeding disorders or atrial fibrillation, Dreyling concluded.