What are the diagnosis and treatment options for Chronic Lymphocytic Leukemia (CLL)?

From the Guidelines

Chronic Lymphocytic Leukemia (CLL) diagnosis requires a complete blood count showing lymphocytosis (>5,000 B-lymphocytes/μL) and flow cytometry confirming the characteristic immunophenotype of CD5+, CD19+, CD23+ B-cells with dim surface immunoglobulin expression. Treatment is not always necessary at diagnosis, as many patients can be managed with "watch and wait" if they are asymptomatic.

Key Considerations

• Treatment is indicated when patients develop significant symptoms, progressive cytopenias, bulky lymphadenopathy, or constitutional symptoms like weight loss or night sweats.
• First-line treatment options include BTK inhibitors (ibrutinib 420mg daily, acalabrutinib 100mg twice daily) or venetoclax (target dose 400mg daily) plus obinutuzumab for most patients, as recommended by the NCCN guidelines 1.
• For fit patients without TP53 mutations, FCR (fludarabine, cyclophosphamide, rituximab) remains an option.
• For relapsed/refractory disease, switching drug classes is recommended, such as moving from a BTK inhibitor to venetoclax or vice versa.
• Genetic testing for TP53 mutations and IGHV mutational status is crucial for treatment selection, as patients with TP53 abnormalities have poorer outcomes with chemoimmunotherapy and should receive targeted agents 1.

Monitoring and Follow-up

• Regular monitoring includes blood counts every 3-6 months and clinical evaluation for disease progression, with treatment adjustments based on response and tolerability.
• Follow-up of asymptomatic patients should include a blood cell count every three months, as well as regular examinations of lymph nodes, liver, and spleen, with special attention to the appearance of autoimmune cytopenias 1.

From the FDA Drug Label

1 INDICATIONS & USAGE

1.1 Chronic Lymphocytic Leukemia (CLL) VIVIMUSTA is indicated for the treatment of adult patients with chronic lymphocytic leukemia.

1 INDICATIONS AND USAGE

1. 2 Chronic Lymphocytic Leukemia (CLL) RITUXAN, in combination with fludarabine and cyclophosphamide (FC), is indicated for the treatment of adult patients with previously untreated and previously treated CD20-positive CLL.

The diagnosis of Chronic Lymphocytic Leukemia (CLL) is not explicitly stated in the provided drug labels. Treatment options for CLL include:

• Bendamustine (PO) for adult patients with CLL, although efficacy relative to first-line therapies other than chlorambucil has not been established 2
• Rituximab (IV) in combination with fludarabine and cyclophosphamide (FC) for adult patients with previously untreated and previously treated CD20-positive CLL 3

From the Research

Diagnosis of Chronic Lymphocytic Leukemia (CLL)

• The diagnosis of CLL is confirmed by the presence of more than 5000 B-lymphocytes/µl and the expression of typical surface markers CD5, CD19, and CD23, which is confirmed by flow cytometry 4.
• Imaging studies such as X-ray of the chest, ultrasound of the abdomen, or CT scan are used to assess the degree of lymphadenopathy or organomegaly 4.
• A bone marrow biopsy is not mandatory for the diagnosis of CLL 4.

Staging of CLL

• The European Binet staging system divides CLL into 3 stages (A, B, and C) based on the degree of lymphadenopathy, organomegaly, and blood counts 4.
• Patients in Binet stage A have 0 to 2 areas of node or organ enlargement with normal levels of hemoglobin and platelets.
• Binet stage B patients have 3 to 5 areas of node or organ enlargement and normal or slightly decreased levels of hemoglobin and platelets.
• Binet stage C patients have anemia and/or thrombocytopenia, with or without lymphadenopathy or organomegaly.

Treatment Options for CLL

• Asymptomatic patients with early-stage CLL (Binet stage A and B) are usually not treated but are followed on a "watch and wait" principle 4, 5, 6.
• Treatment indications include stage Binet C or signs of an active disease, such as rapidly progressive lymphadenopathy or organomegaly, B symptoms, or rapidly deteriorating blood values 4.
• The standard treatment for CLL is immunochemotherapy with fludarabine, cyclophosphamide, and the CD20-antibody rituximab (FCR) for previously untreated and physically fit patients 4.
• Alternative regimens include the combination of bendamustine and rituximab (BR) or the oral drug chlorambucil with or without rituximab for physically compromised patients 4, 5.
• Targeted therapy with B-cell receptor signaling inhibitors, such as ibrutinib, or BCL2 antagonists, such as venetoclax, is also effective in treating CLL, especially in patients with 17p deletion or TP53 mutation 5, 6, 7.
• Allogeneic stem cell transplantation is limited to a small group of patients with high-risk CLL and should be discussed in a high-risk situation, such as 17p deletion or lack of response to standard therapy 4.