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Targeting the B-cell receptor pathway with covalent, irreversible inhibitors of Bruton's tyrosine kinase (BTK) is integral to current treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), although resistance often develops due to mutation of C481 in the BTK binding site. Investigators now report an industry-sponsored, multinational, single-arm, phase 1–2 study of the oral, noncovalent, reversible BTK inhibitor pirtobrutinib in 317 patients with relapsed or refractory CLL/SLL.
Among the 247 patients who had previously received a covalent BTK inhibitor, the median number of prior lines of therapy was 3 (range, 1–11); 41% had also received a B-cell lymphoma 2 (BCL2) inhibitor, and most had also received an anti-CD20 mo…