Dr Phillips on the Investigation of Acalabrutinib/Benendamustine/Rituximab in MCL

Tycel Phillips, MD, MPH, associate clinical professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses the safety and efficacy of acalabrutinib (Calquence) plus bendamustine (Treanda) and rituximab (Rituxan) from a phase 1 trial (NCT02717624) in patients with treatment-naive and relapsed/refractory mantle cell lymphoma (MCL).

Investigators presented data from the phase 1 trial at the 2023 ASCO Annual Meeting, sharing findings from 2 cohorts of patients who were treatment naïve (n = 18) and relapsed/refractory (n = 20). Patients in the treatment-naïve cohort experienced an overall response rate (ORR) of 94.4% (95% CI, 72.7%-99.9), including a complete response (CR) rate of 77.8% per Lugano criteria. Patients in the relapsed/refractory cohort achieved an ORR of 85.0% (95% CI, 62.1%-96.8%) with a CR rate of 70%. Among all patients, the ORR was 89.5% (95% CI, 75.2%-97.1%) with a CR rate of 73.7%.

BTK inhibitors, such as acalabrutinib, have provided a benefit for patients with relapsed/refractory MCL, Phillips says. Because of this benefit in later lines of therapy, BTK inhibitors have also been explored in the frontline treatment, with the goal of augmenting the benefit seen with chemoimmunotherapy and a single- agent therapy, Phillips explains. Therefore, the goal of this phase 1 trial was to evaluate the safety and efficacy derived by combining these 3 agents in different settings for patients with MCL, Phillips notes.

This approach was similar to what was seen with ibrutinib (Imbruvica), which was combined with bendamustine and rituximab in the phase 3 SHINE trial (NCT01776840). However, since acalabrutinib, a second generation BTK inhibitor, has a more selective design and less off-target effects, and the goal was to examine if this could be an efficacious and safe approach, Phillips notes.

Bendamustine and rituximab are typically used as standard chemoimmunotherapy used for patients with MCL, particularly in those who are considered to be unfit or intolerant for an autologous stem cell transplant and those who are typically 65 and older, since because bendamustine is not associated with cause cardiac toxicity or neuropathy, and is generally well tolerated, Phillips concludes.