Onkológia 2/2024
The genetic profile is determinating the choice of treatment of de-novo patients with chronic lymphocytic leukemia
Chronic lymphocytic leukemia (CLL) is a disease with an extremely variable clinical course. Diagnosis and, above all, treatment must be individualized not only taking into account the patient›s age, general condition, associated diseases and treatment goals, but it is also important to know the biology of the disease and prognostic and predictive factors of treatment. The advent of targeted drugs - oral inhibitors of signaling pathways (ibrutinib, acalabrutinib and venetoclax) - together with the development of monoclonal antibodies enabled CLL patients to achieve deeper remission and changed the current therapeutic procedures and treatment goals, leading to a significant improvement in the quality and length of life of CLL patients. Different treatment strategies are available for the first-line treatment of CLL. ESMO (European Society for Medical Oncology) guidelines from 2020, which significantly divide patients into fit and unfit group, are gradually losing their relevance. Various biological and genetic markers have their prognostic significance and thus are essential in choosing a treatment strategy. Del 17p, TP53 mutation, as well as unmutated IGHV status predict aggressive disease course, resistance to chemoimmunotherapy (CIT) and shorter time to progression. These patients should be indicated in the first line for continuous treatment with Bruton›s tyrosine kinase (BTK) inhibitors acalabrutinib or ibrutinib until disease progression or for time-limited treatment with a combination of venetoclax and obinutuzumab, or most recently also ibrutinib and venetoclax. In addition to the mentioned risk factors, the choice of treatment depends also on age, performance status, comorbidities, chronic medication and patient preference. In the article, we provide an overview of the treatment recommendations according to the Spanish working group GELLC (Grupo Español de leukemia lymphocitica cronica), the German recommendations according to Oncopedia and the American NCCN (National Comprehensive Cancer Network) guidelines.
Keywords: chronic lymphocytic leukemia, acalabrutinib, ibrutinib, venetoclax
