Acalabrutinib, a second-generation bruton tyrosine kinase (Btk) inhibitor, in previously untreated chronic lymphocytic leukemia (CLL).

7521Background: Btk is a kinase involved in B-cell receptor signaling and a critical therapeutic target in CLL. Acalabrutinib—an irreversible, selective Btk inhibitor has demonstrated clinical efficacy in relapsed CLL (Byrd NEJM 2015). Here, we present preliminary results from an ongoing Phase 1-2 study of acalabrutinib monotherapy in patients (pts) with previously untreated CLL. Methods: Pts with previously untreated CLL who met IWCLL 2008 criteria for treatment were eligible, irrespective of any cytopenias. Pts received oral acalabrutinib at 100 mg BID (n=37) or 200 mg QD (n=37). Pts had a median age of 64 (48-85) years, bulky lymph nodes ≥ 5 cm (47%) and unmutated IGHV gene (57%, 38/67). CLL responses were assessed per modified IWCLL criteria. Results: Results are presented through 07Dec2015 for the first 74 treated pts, including 72 evaluable for response. Median time on study (N=74) was 11 (1-15) months. Acalabrutinib was well tolerated with 97% (72/74) of pts continuing on study drug. Most AEs were ...