Pirtobrutinib for mantle cell lymphoma

Pirtobrutinib is currently in clinical development for mantle cell lymphoma (MCL). MCL is a rare type of non-Hodgkin lymphoma (NHL) that usually behaves like a fast-growing lymphoma. It develops when B-cells, white blood cells, become abnormal. The abnormal B-cells usually build up in lymph nodes, but they can affect other parts of the body. MCL often responds well to frontline chemotherapy but the responses are not durable and often of relatively short duration. Once MCL has entered the relapsed/refractory stage, it becomes more difficult to treat and patients deteriorate at an increasing pace.
Pirtobrutinib is expected to work by reversibly binding to a protein that is critical for the survival and growth of tumour cells; this will inhibit its action, killing tumour cells. Previous inhibitors have been particularly efficacious but due to permanent binding, resistance and intolerance have occurred, so their use must be stopped. In contrast, pirtobrutinib reversibly binds which suggests intolerance and resistance are less likely. If licensed, pirtobrutinib, given orally, will offer an additional second-line or greater treatment for patients with relapsed or refractory MCL who have received prior Bruton's tyrosine kinase (BTK) treatment.