Onkologie. 2023:17(4):273-281 | DOI: 10.36290/xon.2023.052

Modern approach to the treatment of chronic lymphocytic leukemia

Lukáš Smolej

IV. interní hematologická klinika, Fakultní nemocnice v Hradci Králové

Lékařská fakulta Univerzity Karlovy v Hradci Králové

Chronic lymphocytic leukemia (CLL) is the most common lymphoid malignancy of adults in the Euro-American population and predominantly affects the elderly: the median age at diagnosis is between 65 and 72 years. Most patients are nowadays diagnosed at an early asymptomatic stage and do not require treatment. The heterogeneity of the prognosis of CLL is extraordinary. Even with long-term follow-up, about 50% of CLL patients do not progress and never require treatment, which is initiated only in case of the disease´s clinical activity. Prognostic factors, especially TP53 gene deletion/mutation, other cytogenetic abnormalities, and mutation status of the immunoglobulin heavy chain variable region (IGHV) are very useful in refining the prognosis of individual patients. These markers can also help to tailor the treatment, thus becoming predictive factors. The therapeutic approach to CLL has undergone truly revolutionary changes over the last 20 years: from chemotherapy to chemoimmunotherapy through addition of the anti-CD20 monoclonal antibodies rituximab or obinutuzumab, which for the first time in the history of CLL treatment has led to prolonged overall survival, to new, oral targeted agents, in particular regimens based on the BCL-2 inhibitor venetoclax with an anti-CD20 antibody and the Bruton's tyrosine kinase inhibitors ibrutinib and acalabrutinib. These targeted inhibitors are now considered the standard choice for relapsed/refractory CLL and have largely replaced chemoimmunotherapy from first-line treatment in the vast majority of patients as well. Chemoimmunotherapy (especially the combination fludarabine-cyclophosphamide-rituximab [FCR] in younger fit patients without comorbidities) can still be considered as a treatment alternative in a selected group of previously untreated patients with a biologically highly very favourable prognosis (mutated IGHV gene and favourable cytogenetics, e.g. del 13q).

Keywords: chronic lymphocytic leukemia, chemoimmunotherapy, targeted inhibitors, venetoclax, ibrutinib, acalabrutinib, rituximab, obinutuzumab, minimal residual disease.

Accepted: October 3, 2023; Published: October 5, 2023  Show citation