Venetoclax, a highly selective, oral B-cell lymphoma 2 inhibitor, provides a robust targeted-therapy option for the treatment of chronic lymphocytic leukemia (CLL), including patients with high-risk del(17p)/mutated-TP53 and immunoglobulin heavy variable region unmutated CLL and those refractory to chemoimmunotherapy across all age groups. Due to the potent pro-apoptotic effect of venetoclax, treatment initiation carries a risk of tumor lysis syndrome (TLS). Prompt and appropriate management is needed to limit clinical TLS, which may entail serious adverse events and death. Venetoclax ramp-up involves gradual, stepwise increases in daily venetoclax dosing from 20 mg to 400 mg (target dose) over 5 weeks; adherence to on-label scheduling provides a tumor debulking phase, reducing the risk of TLS. The key components of safe venetoclax therapy involve assessment (radiographic evaluation and baseline blood chemistry), preparation (adequate hydration), and initiation (blood chemistry monitoring). In addition to summarizing the evidence for venetoclax's efficacy and safety, this review uses hypothetical patient scenarios based on risk level for TLS (high, medium, low) to share the authors' clinical experience with venetoclax initiation and present global approaches utilized in various treatment settings. These hypothetical scenarios highlight the importance of a multidisciplinary approach and shared decision-making, outlining best practices for venetoclax initiation and overall optimal treatment strategies in patients with CLL.
Keywords: chronic lymphocytic leukemia; multidisciplinary; obinutuzumab; onboarding; ramp-up; rituximab; tumor lysis syndrome; venetoclax.