Enrichment of BTK Leu528Trp mutations in Patients with CLL on Zanubrutinib: Potential for Pirtobrutinib Cross Resistance
Research Article | Piers Blombery, Ella R Thompson, Thomas E Lew, Ing Soo Tiong, Rory Bennett, Chan Y Cheah, Katharine Louise Lewis, Sasanka M Handunnetti, Chloe Pek Sang Tang, Andrew Roberts, John F. Seymour, Constantine S. Tam; Enrichment of BTK Leu528Trp mutations in Patients with CLL on Zanubrutinib: Potential for Pirtobrutinib Cross Resistance.
Relevance: We describe 2 patients with BTK Leu528Trp mutations who showed clinical cross-resistance and progressive enrichment of the BTK Leu528Trp mutation over time when treated with the non-covalent BTK inhibitor pirtobrutinib. Both patients subsequently responded to venetoclax based treatment. In summary we have identified an enrichment of the BTK Leu528Trp mutation arising in patients treated with zanubrutinib which may impart cross-resistance to the non-covalent inhibitor pirtobrutinib and therefore implications for sequencing of these treatments in CLL.