The options for frontline chronic lymphocytic leukemia (CLL) treatment continue to expand. Therapies include monotherapy with a Bruton's tyrosine kinase inhibitor (BTKi), doublet therapies such as venetoclax with intravenous obinutuzmab or an oral BTKi, and triplet therapy combining BTKi, venetoclax, and CD20 antibody. Treatment duration also is increasingly variable, from fixed duration to utilization of undetectable minimal residual disease (uMRD) to determine optimal treatment completion. Currently, the best option for an individual patient requires a multifaceted approach considering the individual's cytogenetics, comorbidities, and personal preferences, including time-limited therapy vs continuous treatment. In this article, we outline the current state of frontline CLL including ongoing questions and future directions.

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