Individualizing Frontline CLL: Choosing Between Continuous and Fixed-Duration BTK Inhibitor-Based Strategies

Frontline management of chronic lymphocytic leukemia (CLL) has shifted from chemoimmunotherapy to targeted regimens, leaving clinicians to choose between continuous and fixed-duration approaches. In this program, expert faculty compare covalent and noncovalent Bruton tyrosine kinase (BTK) inhibitors, including acalabrutinib, zanubrutinib, and pirtobrutinib, and weigh venetoclax plus obinutuzumab against all-oral acalabrutinib plus venetoclax from the AMPLIFY trial. The discussion covers low tumor lysis risk with a BTK inhibitor lead-in, infusion reactions, infection and cardiac toxicity with continuous therapy, and how patient preference, comorbidities, cost, and access shape decisions. Through patient cases, the faculty address high-risk chromosomal aberrations, the role of an obinutuzumab triplet in younger patients with unmutated immunoglobulin heavy chain variable region (IGHV) disease, retreatment after time-limited therapy, BTK inhibitor sequencing, and emerging head-to-head trials. They conclude that most patients can now receive individualized, well-tolerated therapy.