Treatment of Chronic Lymphocytic Leukemia After Discontinuation of Bruton’s Tyrosine Kinase Inhibitors

Bruton's tyrosine kinase inhibitors (BTKis), including ibrutinib and acalabrutinib, have revolutionized the treatment of patients with chronic lymphocytic leukemia (CLL). These novel agents have led to improved response rates and survival for CLL patients, including those with unmutated immunoglobulin heavy-chain variable region gene (IGHV) or TP53 aberrant CLL.1-14 The oral covalent, irreversible BTKis ibrutinib and acalabrutinib are approved standard-of-care therapies in both front-line4,8,10,11 and relapsed and/or refractory settings.5,9,13 Additionally, clinical trials of the covalent BTKi zanubrutinib recently have shown excellent overall response rates of 94.5% in previously untreated CLL patients with deletion 17p (del17p)15 and 84.6% in relapsed and/or refractory CLL patients.16 Long-term follow-up data have shown that treatment with ibrutinib leads to durable responses for many patients. In 6-year follow-up from the phase 3 RESONATE trial