Treatment of Chronic Lymphocytic Leukemia (CLL)

Initial Management and Diagnosis

The European Society for Medical Oncology recommends observation with monitoring every 3-12 months for asymptomatic patients with early-stage CLL, as early treatment does not improve survival 1, 2
Blood counts and clinical examinations should be performed every 3-12 months after the first year for patients with early-stage CLL 1
No routine imaging is recommended during the watch-and-wait period unless clinical symptoms develop 1

The International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for active disease include significant B-symptoms, cytopenias, massive or progressive lymphadenopathy, progressive lymphocytosis, and autoimmune anemia or thrombocytopenia poorly responsive to corticosteroids 1, 2, 3

The National Comprehensive Cancer Network (NCCN) recommends FISH for del(17p) and TP53 mutation testing before initiating therapy, as it fundamentally changes treatment selection 1, 3
IGHV mutational status should be determined to guide treatment selection, with time-limited or continuous therapy preferred based on mutational status 1, 3
Patient fitness assessment, including comorbidities, renal function, and performance status, should be performed before treatment 4, 5

For patients with del(17p) or TP53 mutation, the European Society for Medical Oncology recommends second-generation covalent BTK inhibitors administered continuously until progression 1, 2
For patients without del(17p)/TP53 mutation, time-limited therapy with venetoclax plus obinutuzumab is the preferred first-line option for those with mutated IGHV status 1, 2
For patients without del(17p)/TP53 mutation and unmutated IGHV status, both continuous BTK inhibitor therapy and time-limited venetoclax plus obinutuzumab are valid first-line options 1, 2

If relapse occurs ≥24-36 months after chemoimmunotherapy or ≥12 months after venetoclax-based therapy, the first-line regimen may be repeated 4, 5
If relapse occurs earlier, switch to an alternative drug class, such as BTK inhibitors or venetoclax-based regimens 4, 1

For young, physically fit patients with del(17p)/TP53 mutation who progress on BTK inhibitors, alemtuzumab followed by allogeneic stem cell transplantation should be considered within clinical trials 4
Del(17p) or TP53 mutation confers the poorest prognosis with median overall survival of 2-3 years with conventional therapy 4, 5

The American Society of Clinical Oncology (ASCO) recommends against treating asymptomatic early-stage patients, as this does not improve survival and exposes patients to unnecessary toxicity 5, 1
Chemoimmunotherapy should not be used in del(17p)/TP53 mutated patients, as they have very short progression-free survival even with FCR 4, 5
TP53 abnormalities should be retested before each line of therapy, as clonal evolution can occur 1