Fateeha Furqan, MD, Discusses Pirtobrutinib Plus CAR-T

Dr. Furqan, third-year oncology fellow at Medical College of Wisconsin, shared data from a retrospective analysis on 11 patients who received pirtobrutinib, a Bruton’s tyrosine kinsase (BTK) inhibitor, prior to chimeric antigen receptor T-cell (CAR-T) therapy.

“We did this study because there is some recent data showing that combining BTK inhibitors with CAR-T cell therapy improved outcomes,” Dr. Furqan said. “Most of this data comes from CLL and in CLL they have combined ibrutinib which is a covalent not very selective BTK inhibitor with the anti-CD19 CAR-T cell therapy.”

Preclinical data has shown that ibrutinib and zanubrutinib improve CAR-T therapy via decreased expression of T-cell exhaustion markers and improved CAR-T cell therapy effect overall, according to Dr. Furqan.

“There is clinical data in CLL that showed patients who received ibrutinib with anti-CD19 CAR-T cell therapy did pretty well, although they were small studies,” Dr. Furqan said. “But in these studies there was an increased signal towards toxicity, particularly cardiotoxicity.”

“That’s why we chose pirtobrutinib, which is a highly selective BTK inhibitor and it doesn’t have a lot of cardiotoxicity like the rest of the BTK inhibitors have,” Dr. Furqan continued.

Based on their findings, Dr. Furqan suggested that “BTK inhibition with pirtobrutinib can improve the CAR-T product itself in terms of polyfunctionality and can eventually improve outcomes of CAR-T cell therapy.”

In closing, Dr. Furqan added that a clinical trial combining pirtobrutinib with CAR-T cell therapy as a bridging therapy followed by pirtobrutinib maintenance is opening up at the Medical College of Wisconsin.