Dr Koff on the Role of Covalent BTK Inhibitors and Pirtobrutinib in MCL

Jean L. Koff, MD, MS, associate professor, Department of Hematology and Medical Oncology, Emory University School of Medicine, discusses the role of covalent BTK inhibitors in the treatment of mantle cell lymphoma (MCL).

Covalent BTK inhibitors are increasingly recommended as part of frontline therapy and maintenance regimens in MCL, particularly in patients suitable for aggressive induction approaches, Koff notes. Agents such as ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa) have shown efficacy in MCL, leading to improved response rates and progression-free survival; However, despite their efficacy, some patients eventually develop resistance or intolerance to these covalent BTK inhibitors, she adds.

In January 2023, the FDA approved pirtobrutinib (Jaypirca) for the treatment of adult patients with relapsed/refractory MCL who have undergone at least 2 lines of systemic therapy, including a covalent BTK inhibitor.

Pirtobrutinib, a noncovalent BTK inhibitor, has emerged as a therapeutic option for patients with MCL following treatment with 1 of the approved covalent agents, Koff explains. She highlights that pirtobrutinib has demonstrated clinically meaningful efficacy across various MCL subgroups, including those who have developed resistance to or have previously been treated with covalent BTK inhibitors. Moreover, there is emerging evidence suggesting that pirtobrutinib may be effective even in patients who have not been exposed to any prior BTK inhibitors, expanding its potential utility in MCL treatment, she says.

Pirtobrutinib has been well tolerated, and it has been associated with low rate of treatment discontinuation due to drug-related toxicities, which makes it a favorable option in the MCL treatment landscape, Koff explains. This safety profile supports its integration into clinical practice, providing an effective alternative for patients who may not tolerate other BTK inhibitors.

Pirtobrutinib should be considered a new standard of care for patients with MCL who have received prior covalent BTK inhibitors, she continues. Its safety and efficacy profile make it an important addition to the therapeutic options available for managing MCL, particularly in the context of relapsed or refractory disease, Koff concludes.