BTK Inhibitors in R/R CLL: Navigating Options and Tailoring Treatment

Panelists discuss how fixed-duration options like venetoclax plus obinutuzumab show promise in treating chronic lymphocytic leukemia (CLL) by offering defined treatment periods rather than indefinite therapy.

Panelists discuss how pirtobrutinib demonstrated superior progression-free survival compared with standard Bruton tyrosine kinase (BTK) inhibitors in previously treated chronic lymphocytic leukemia (CLL) patients as shown in the BRUIN CLL-321 trial results.

Panelists discuss how emerging data from ASH 2024 and recent NCCN guidelines supporting pirtobrutinib use in later-line CLL treatment are prompting oncologists to carefully evaluate factors like BTK resistance patterns and the potential role of novel BTK degraders when selecting therapy for relapsed/refractory patients.

Panelists discuss how strategic sequencing decisions in frontline CLL therapy, informed by new evidence from the Rhodes et al. ASH 2024 study, have downstream implications for managing treatment options in the relapsed/refractory setting.

Panelists discuss how Bruton tyrosine kinase (BTK) inhibitor selection in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) depends on key factors including prior therapy response, BTK C481 mutation status, comorbidities, drug interaction profiles, dosing convenience, and adverse effect considerations, with noncovalent inhibitors offering particular benefit for those with BTK mutations or intolerance to covalent agents.

Panelists discuss how distinct safety profiles among Bruton tyrosine kinase (BTK) inhibitors—including variations in cardiovascular effects, bleeding risk, infection susceptibility, and other adverse events—guide personalized treatment decisions in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) based on individual comorbidities and risk factors.

Panelists discuss how the inclusion of ibrutinib on the Inflation Reduction Act (IRA) negotiated drug price list could make it a more economically attractive first-line option, potentially influencing the sequencing of Bruton tyrosine kinase (BTK) inhibitors in relapsed/refractory chronic lymphocytic leukemia (R/R CLL) treatment while considering other financial factors like insurance coverage, copays, and total out-of-pocket costs that impact patient access and treatment decisions.

Panelists discuss how decisions to switch between Bruton tyrosine kinase (BTK) inhibitors are driven by multiple factors including intolerable toxicities, development of resistance mutations, disease progression, drug interactions, and patient preferences, with pirtobrutinib emerging as a particularly valuable option for patients with BTK C481 mutations or those who have exhausted other BTK inhibitor (BTKi) options.

Panelists discuss how data from Mansour and colleagues suggesting potential Bruton tyrosine kinase (BTK) inhibitor discontinuation after 2+ years of therapy opens up new treatment strategy considerations, with decisions between discontinuation vs switching to alternative BTK inhibitor (BTKi) therapy being influenced by factors such as depth and duration of response, toxicity severity, patient preferences regarding adverse effects and treatment schedules, and quality-of-life considerations.

Panelists discuss how successful transitions between Bruton tyrosine kinase (BTK) inhibitors require careful management of multiple challenges including optimal timing of the switch, potential washout periods, dose adjustments, patient education about expected adverse effects, and close monitoring during the transition period to maintain treatment efficacy while minimizing complications.

Panelists discuss how the relapsed/refractory chronic lymphocytic leukemia treatment landscape evolved significantly in 2024 with expanded Bruton tyrosine kinase inhibitor options, growing real-world evidence for newer agents, and emerging combination strategies, while expressing optimism for future advances in personalized therapy approaches and novel drug development.