Importance
Chronic lymphocytic leukemia (CLL), defined by a minimum of 5 × 10 9 /L monoclonal B cells in the blood, affects more than 200,000 people and is associated with approximately 4,410 deaths in the US annually. CLL is associated with an immunocompromised state and a higher rate of complications from infections.
Observations
At diagnosis, the median age of patients with CLL is 70 years, and it is estimated that 95% of patients have at least one medical comorbidity .
Approximately 70% to 80% of patients with chronic lymphocytic leukemia (CLL) are asymptomatic at the time of diagnosis and one third will never require treatment for CLL. Prognostic models have been developed to estimate time to first treatment and overall survival, but for asymptomatic patients, regardless of disease risk category, clinical observation is the standard of care .
Treatment should be offered to patients with symptomatic disease who have bulky or progressive lymphadenopathy or hepatosplenomegaly and those with low neutrophil counts, anemia or thrombocytopenia and/or symptoms of fever, heavy night sweats and weight loss (symptoms B).
For these patients, first-line treatment consists of a regimen containing a covalent Bruton’s tyrosine kinase (BTK) inhibitor (acalabrutinib, zanubrutinib, or ibrutinib) or a B-cell leukemia/lymphoma 2 (BCL2) inhibitor ( venetoclax). There is no evidence that starting either class before the other improves results. Covalent BTK inhibitors are typically used indefinitely.
Survival rates are approximately 88% at 4 years for acalabrutinib, 94% at 2 years for zanubrutinib, and 78% at 7 years for ibrutinib. Venetoclax is prescribed in combination with obinutuzumab, an anti-CD20 monoclonal antibody, as first-line treatment for 1 year (overall survival, 82% at 5-year follow-up).
A noncovalent BTK inhibitor, pitobrutinib, has shown an overall response rate of more than 70% after failure of covalent BTK inhibitors and venetoclax. Phosphoinositide 3′-kinase (PI3K) inhibitors (idelalisib and duvelisib) can be prescribed for disease that progresses on BTK inhibitors and venetoclax, but patients require close monitoring for adverse events, such as autoimmune diseases and infections. .
In patients with multiple relapses , chimeric antigen receptor T-cell therapy (CAR-T) with lipocabtagene maraleucel was associated with a complete response rate of 45%.
The only potential cure for chronic lymphocytic leukemia (CLL) is allogeneic hematopoietic cell transplantation, which remains an option after the use of targeted agents. Chimeric antigen receptor T-cell therapy (CAR-T) with lipocabtagene maraleucel was associated with a complete response rate of 45%.
Conclusions and relevance
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