Dr Cohen on Treatment Considerations for Relapsed/Refractory MCL

Jonathon B. Cohen, MD, MS, associate professor, Department of Hematology and Medical Oncology, codirector, Lymphoma Program, university chair, Data and Safety Monitoring Committee, Winship Cancer Institute, Emory University School of Medicine, discusses treatment considerations for patients with relapsed/refractory mantle cell lymphoma (MCL), highlighting the role of pirtobrutinib (Jaypirca) in the early management of this disease.

During the 2023 ASH Annual Meeting, updated results from the phase 1/2 BRUIN study (NCT03740529) of pirtobrutinib in previously treated patients with relapsed/refractory MCL were presented. Historically, patients previously treated with a covalent BTK inhibitor have faced dismal outcomes, Cohen begins. In the current MCL treatment paradigm, pirtobrutinib has emerged as a viable treatment option, and is FDA approved for patients who have progressed following covalent BTK inhibitor therapy or discontinued treatment due to intolerance, he explains.

Additionally, CD19-directed CAR T-cell therapy may be considered for patients with MCL. However, although brexucabtagene autoleucel (brexu-cel; Tecartus) yields a high overall response rate and sustained response for patients achieving a complete response, it is not suitable for all patients due to its intensity, Cohen emphasizes.

When managing relapsed MCL, especially in patients ineligible for covalent BTK inhibitor therapy, treatment decisions hinge on individual patient status and comorbidities, he expands. The prognosis for BTK inhibitor–pretreated patients with MCL has historically been bleak, he says, adding that the approval of pirtobrutinib provides a treatment option for this patient subgroup that is less intensive compared with CAR T-cell therapy. There is considerable interest in investigating whether pirtobrutinib could play a role in earlier MCL management, Cohen states.

Although pirtobrutinib has generated good tolerability and activity in patients with MCL previously treated with covalent BTK inhibitors, updates shared at the 2023 ASH Annual Meeting regarding pirtobrutinib's efficacy in BTK inhibitor–naive patients are also promising, he continues. The large phase 3 BRUIN-MCL-321 trial (NCT04662255) is underway to ascertain whether a noncovalent BTK inhibitor such as pirtobrutinib might be preferable over covalent BTK inhibitors for BTK inhibitor–naive patients, Cohen reports. This trial represents a significant advancement in evaluating pirtobrutinib and determining its optimal placement within the broader treatment armamentarium for MCL, he concludes.