From the Guidelines
Chronic lymphocytic leukemia (CLL) treatment should be based on the disease stage, patient’s age and overall fitness, and cytogenetic abnormalities, with a focus on targeted therapies such as BTK inhibitors or BCL-2 inhibitors for patients with indications for initiating treatment, as recommended by the NCCN Guidelines 1.
Overview of CLL
Chronic lymphocytic leukemia (CLL) is a slow-growing cancer of white blood cells that primarily affects older adults, with a median age at diagnosis of 72 years 1. It develops when abnormal lymphocytes accumulate in the blood, bone marrow, and lymphatic tissues.
Diagnosis and Symptoms
Diagnosis involves blood tests showing elevated lymphocyte counts, flow cytometry to identify characteristic cell markers, and sometimes bone marrow biopsy. Common symptoms include fatigue, enlarged lymph nodes, frequent infections, night sweats, and weight loss.
Treatment Options
Treatment depends on disease stage, with early-stage CLL often managed through watchful waiting rather than immediate intervention. When treatment is necessary, standard options include chemoimmunotherapy regimens like FCR (fludarabine, cyclophosphamide, rituximab) or targeted therapies such as BTK inhibitors (ibrutinib, acalabrutinib) or BCL-2 inhibitors (venetoclax) 1.
Prognosis and Monitoring
Prognosis varies widely based on genetic factors, with some patients living decades with minimal treatment while others require more aggressive management. Regular monitoring of blood counts and symptoms is essential for all CLL patients, even during watchful waiting periods, to detect disease progression requiring intervention. Measurable residual disease (MRD) is a sensitive reflection of disease burden during and after fixed-duration treatment and has been correlated with progression-free and overall survival 1.
Key Considerations
The selection of treatment should be based on the disease stage, patient’s age and overall fitness, and cytogenetic abnormalities, with a focus on targeted therapies for patients with indications for initiating treatment 1.
From the Research
Overview of Chronic Lymphocytic Leukemia
- Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the blood and bone marrow, characterized by the production of an excessive number of immature white blood cells 2.
- The disease typically occurs in older patients and has a highly variable clinical course 2.
- Leukemic transformation is initiated by specific genomic alterations that interfere with the regulation of proliferation and apoptosis in clonal B-cells 2.
Diagnosis and Prognosis
- The diagnosis of CLL is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes 2.
- Two clinical staging systems, Rai and Binet, provide prognostic information by using the results of physical examination and blood counts 2.
- Various biological and genetic markers, such as deletions of the short arm of chromosome 17 (del(17p)) and/or mutations of the TP53 gene, provide additional prognostic information 2.
Treatment Options
- Only patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy 2.
- Treatment options include combinations of the BCL2 inhibitor venetoclax with obinutuzumab, or venetoclax with ibrutinib, or monotherapy with one of the inhibitors of Bruton tyrosine kinase (BTK) 2.
- The addition of rituximab to fludarabine and cyclophosphamide has been shown to improve progression-free survival and overall survival in patients with CLL 3.
- Fludarabine and cyclophosphamide combination regimen has been shown to be effective in patients with CLL, with a significant advantage over single-agent fludarabine in the salvage setting 4.
Ongoing Research and Future Directions
- Ongoing clinical trials are investigating the use of novel agents in patients with early-stage CLL 5.
- The optimal sequencing of targeted therapies remains to be determined 2.
- A medical challenge is to treat patients who are double-refractory to both BTK and BCL2 inhibitors, who need to be treated within experimental protocols using novel drugs 2.