Patients Resistant to Covalent BTK Inhibitors Remain a Challenge in MCL

Michael Wang, MD, Puddin Clarke endowed professor of lymphoma and myeloma at The University of Texas MD Anderson Cancer Center, discusses where unmet needs still exist for patients with relapsed/refractory mantle cell lymphoma (MCL).

According to Wang, patients who are resistant to covalent Bruton’s tyrosine kinase (BTK) inhibitors often remain a challenge to treat. While they are typically treated using chimeric antigen receptor (CAR) T-cell therapies that produce high efficacy, these agents also often produce high toxicity rates as well.

Wang also notes the potential role of pirtobrutinib (Jaypirca), a highly selective kinase inhibitor, for these patients. The agent was granted FDA approval for patients with relapsed/refractory MCL who previously received at least 2 lines of systemic therapy, including with a BTK, in January 2023.

This approval was based on findings from the phase 1/2 BRUIN trial (NCT03740529) which showed that treatment with pirtobrutinib at 200 mg given once daily until disease progression or unacceptable toxicity elicited an overall response rate of 50% among patients. Additionally, 13% of patients achieved a complete response at time of analysis.

Transcription:

0:10 | There's a huge unmet need when the patient is resistant to covalent BTK inhibitors, and if they have progressed or relapsed, we use CAR T cells because CAR T-cell efficacy is high, but its toxicity is [also] high. So, if the patient had relapsed after BTK inhibitors, they are not high-risk. They have small tumors, and they do not need immediate CAR T-cell therapy. You could put this patient in long-term remission using only pirtobrutinib as shown in the phase 2 clinical trial that has been recently published in the Journal of Clinical Oncology.

0:54 | Other major studies are not only at the phase 3, but other smaller studies with the investigator initiated trials are ongoing.