Dr Dreyling on the Recommended Use of Acalabrutinib Plus BR in Pretreated MCL

"My recommendation for hands-on medicine if and when I apply this combination in patients is that the first thing I reduce is the chemotherapy backbone, specifically bendamustine because it is immunosuppressive, so it may hamper [the feasibility of] subsequent potential treatments."

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

Given that the median age of patients with MCL is typically around 70 years, the historical standard of care (SOC) has been BR due to its better tolerability compared to more intensive regimens, which are often not suitable for this demographic.

Updated data presented at the 2025 EHA Congress showed that patients in the high-risk cohort (n = 187) who received acalabrutinib plus BR achieved a high overall response rate of 89.8% (95% CI, 84.9%-93.6%) and demonstrated a statistically significant progression-free survival (PFS) benefit compared with the placebo arm (unstratified HR, 0.74; P = .0432). Dreyling suggested that the ECHO study has the potential to show an overall survival benefit similar to that observed in the phase 3 TRIANGLE trial (NCT02858258), validating this BTK inhibitor combination approach for the majority of MCL patients (from conversation history).

From a clinical implementation standpoint, Dreyling recommended that the initial adjustment to the regimen should focus on reducing the chemotherapy component. Specifically, he advised reducing the number of bendamustine cycles to four and adjusting the dose per cycle based on the patient's age. This strategy is designed to mitigate late toxicities and address the immunosuppressive nature of bendamustine, thereby preserving options for subsequent potential treatments. Dreyling concluded by emphasizing the importance of clinical research, including independent academic trials like TRIANGLE (NCT02858258) and the phase 2 ENRICH (NCT01880567) study, in improving patient outcomes.