Clinical Outcomes in Patients With CLL Treated With BTKi at a Large US Cancer Center

Area of Science:

• Hematology
• Oncology
• Clinical Research

Background:

• Covalent Bruton's tyrosine kinase inhibitors (BTKi) are used for chronic lymphocytic leukemia (CLL).
• Treatment discontinuation is common, but post-discontinuation outcomes are not well-documented.
• Understanding outcomes after BTKi cessation is crucial for managing CLL patients.

Purpose of the Study:

• To evaluate outcomes in adult patients with CLL after discontinuing covalent BTKi therapy.
• To assess the efficacy of subsequent therapies, particularly B-cell lymphoma 2 inhibitors (BCL2i), post-BTKi.
• To identify clinical needs for patients progressing on or after BTKi and BCL2i treatments.

Main Methods:

• Retrospective chart review of 104 adult CLL patients who discontinued covalent BTKi.
• Analysis of progression-free survival (PFS) and overall survival (OS) from BTKi initiation.
• Evaluation of outcomes for patients receiving subsequent therapies, including BCL2 inhibitors.

Main Results:

• Median PFS from BTKi initiation was 3.2 years; median OS was 8.9 years.
• Over half of patients received subsequent therapies, with 80.6% receiving BCL2 inhibitors.
• Patients treated with both BTKi and BCL2i showed high rates of discontinuation and mortality, indicating limited efficacy in later lines of therapy.

Conclusions:

• Covalent BTKi discontinuation in CLL patients is associated with significant survival metrics but often leads to subsequent treatment needs.
• Subsequent BCL2 inhibitor therapy shows initial response but high rates of discontinuation and death, especially in heavily pre-treated patients.
• There is a critical unmet clinical need for novel treatment strategies for CLL patients who have exhausted BTKi and BCL2i options.