Symposium |Optimizing chronic lymphocytic leukemia management in a changing landscape

On June 22, 2026, the Lymphoma Hub held a virtual symposium, titled Optimizing treatment for chronic lymphocytic leukemia with BTK inhibitors. During the symposium, Lymphoma Hub Steering Committee member Francesc Bosch, Vall d'Hebron Barcelona Hospital Campus, Barcelona, ES, led a case-based presentation and panel discussion on optimizing chronic lymphocytic leukemia (CLL) management in a changing landscape.

During his presentation, Bosch highlights current treatment guidelines for the management of patients with first-line (Figure 1) and relapsed/refractory (R/R; Figure 2) CLL. He also discusses three patient cases and the factors influencing treatment decisions specific to each case. Bosch then chairs a panel discussion featuring Susan O’Brien, University of California Irvine, US; Farrukh Awan, University of Texas Southwestern Medical Center, Dallas, US; and Gilles Salles, Memorial Sloan Kettering Cancer Center, New York, US, covering key aspects of optimizing CLL management.

Key points

• Treatment initiation should be based on the presence of active disease, as defined by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria.¹

  • Early treatment is not indicated, even in patients with high-risk disease, due to the lack of overall survival benefit.⁷

• Key factors to consider when choosing a first-line therapy include TP53 aberrations and IGHV mutational status.¹

• Given the availability of multiple, similarly effective agents for treatment‐naive CLL, treatment selection should be guided by a range of factors beyond drug efficacy alone, such as patient preference, comorbidities, treatment goals, and logistical considerations.¹

• The choice of treatment in R/R CLL is influenced by the type of prior therapy and the reason for treatment discontinuation (progression vs intolerance).¹

• Time‐limited targeted therapies should be preferred over continuous therapy in patients with CLL without TP53 aberrations, while continuous treatment is suggested over time‐limited treatment in patients with TP53 aberrations, unless time‐limited treatment is preferred by shared decision‐making.¹

• The optimal treatment duration and the potential role of measurable residual disease (MRD)-guided treatment are areas of ongoing investigation.⁷

• The optimal sequencing of non-covalent Bruton’s tyrosine kinase inhibitors (BTKis) warrants further evaluation, as the use of covalent BTKis and/or venetoclax-based therapy after non-covalent BTKis has not been prospectively studied.⁸

  • Pirtobrutinib may be a reasonable first-line continuous treatment option for older patients with CLL and comorbidities, given its favorable tolerability and the lower likelihood that multiple subsequent lines of therapy will be needed in this population.⁸ 

This educational resource is independently supported by Eli Lilly and Company. All content is developed by SES in collaboration with an expert steering committee. Funders are allowed no influence.