Dr Burke on Ongoing Investigations of Targeted Therapy Regimens in MCL

John M. Burke, MD, associate chair, Hematology Research Program, US Oncology, medical oncologist/hematologist, Rocky Mountain Cancer Centers, discusses several ongoing or upcoming investigations of targeted therapy in mantle cell lymphoma (MCL).

The field of MCL is increasingly moving towards the use of targeted therapy regimens as a standard treatment approach, with several novel agents showing potential, Burke says. Despite being an integral part of standard practice, these emerging therapeutics call the continued use of chemotherapy in MCL into question, Burke states.

On January 27, 2023, the noncovalent BTK inhibitor pirtobrutinib (Jaypirca) received FDA approval for the treatment of patients with relapsed/refractory MCL following at least 2 lines of systemic therapy, including a covalent BTK inhibitor. The regulatory decision was based on findings from the phase 1/2 BRUIN trial (NCT03740529). Notably, patients in the BTK-naïve subgroup achieved a comparable objective response rate to that of patients given a covalent BTK inhibitor, Burke says.

The ongoing phase 3 BRUIN-MCL-321 trial (NCT04662255) was designed to compare the safety and efficacy of pirtobrutinib with multiple approved BTK inhibitors, including ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa), Burke reports. Patients with previously treated, BTK inhibitor–naïve MCL will be randomly assigned 1:1 to receive either investigator's choice of a standard BTK inhibitor, or oral pirtobrutinib. The study will help determine whether pirtobrutinib is superior to covalent BTK inhibitors in this patient population, Burke says.

Additionally, the addition of acalabrutinib (Calquence) to lenalidomide (Revlimid) and rituximab (Rituxan) is emerging as another promising chemotherapy-free combination in MCL, Burke continues. Findings from a single-arm, phase 2 study (NCT03863184) showed that the triplet regimen produced a high complete response rate when administered in the frontline setting.

Lastly, several trials in MCL are demonstrating early efficacy with venetoclax (Venclexta) plus various BTK inhibitors both with or without CD20 antibodies, Burke concludes.