Pirtobrutinib Adds to the Treatment Armamentarium for MCL

Cyrus M. Khan, MD, hematologist in the Division of Hematology and Cellular Therapy at West Penn Hospital of Allegheny Health Network, discusses pirtobrutinib (Jaypirca) for mantle cell lymphoma (MCL) and the phase 1/2 BRUIN study (NCT03740529).

Pirtobrutinib is a Bruton's tyrosine kinase (BTK) inhibitor that was previously granted approval from the FDA in January 2023, for the treatment of patients with relapsed/refractory MCL who previously received at least 2 lines of systemic therapy, including a BTK inhibitor.

Findings from the phase 1/2 BRUIN study showed the potential of pirtobrutinib for this patient population, leading to its approval. Khan notes that pirtobrutinib offers a new approach to targeting the BTK pathway after a patient has been treated with a covalent BTK inhibitor.

Transcription:

0:10 | The BRUIN study is a larger trial that included many different patients, including [patients with] mantle cell lymphoma. The mantle cell efficacy portion was about 120 patients and these were patients with relapsed/refractory mantle cell lymphoma. All of these patients had already progressed on a prior BTK inhibitor, whether that was ibrutinib [Imbruvica], whether that was acalabrutinib [Calquence], or whether that was zanubrutinib [Brukinsa]. All of the ones that I mentioned are what we call irreversible inhibitors and they form covalent bonds. So what that means is that there is a different bond that it forms on the BTK side at the Cys-481 residue side.

0:49 | We previously discovered that patients who have a mutation at the Cys-481 side progress on these BTK inhibitors because they stopped working. Pirtobrutinib has a different structure, and it doesn't matter whether that Cys-481 mutation is there or not. When it was used in such patients, it still worked. So [there was] great efficacy, an almost 50% response rate, including [complete responses] and [partial responses], a median duration of response of about 8 months or so, and it works in all these pretreated patients. There were even patients with transplants on that trial, and even [chimeric antigen receptor] T-cell therapy. So [it is] a welcome addition to the armamentarium with BTK inhibitors against mantle cell lymphoma.