Title : First line treatment in chronic lymphocytic leukemia – The agony of choice
Abstract:
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western World. Therapeutic options have changed dramatically over the last decade, from ineffective chemotherapy to highly specific small molecules that target crucial pathways in CLL cells. The first available drug was ibrutinib, a Bruton-tyrosine kinase (BTK) inhibitor, that has revolutionized CLL treatment. Ibrutinib is an oral agent that is given indefinitely until disease progression or unacceptable toxicity. Accumulating adverse events over time, and particularly cardiovascular events, limit drug administration. More specific, second generation BTK inhibitors, are currently available, have a superior safety profile and might even be more effective. Another therapeutic option is giving a time-limited course of the BCL2-inhibitor, venetoclax-based treatment. This agent is highly effective and achieves high rates of undetectable minimal residual disease (MRD), allowing discontinuation of venetoclax after a defined course of therapy. The choice between these options depends on patient preferences, patient’s comorbidities, and disease-specific predictive markers, such as immunoglobulin heavy chain (IGHV) rearrangement, deletion 17p, and somatic TP53 mutations. Recently, a time-limited combination of ibrutinib and venetoclax has gained increasing interest, as it may overcome some of the adverse prognostic markers associated with disease progression. In my talk I will discuss the evidence for the various therapeutic regimens, their advantages, and shortcomings, and will present my take on first line CLL management in 2023.
Audience Takeaway:
- Learn about available first line treatment in CLL.
- Will be familiar with recent pivotal studies in CLL.
- Utilize prognostic markers in therapy decision-making.
- Learn concepts to guide choice of therapy.
