From the Research
Approximately two-thirds of patients with chronic lymphocytic leukemia (CLL) will eventually require therapy. While many patients are initially managed with a "watch and wait" approach after diagnosis, the majority will progress to a point where treatment becomes necessary. Disease progression typically manifests as worsening cytopenias, symptomatic or massive lymphadenopathy, splenomegaly, constitutional symptoms (fever, night sweats, weight loss), or a lymphocyte doubling time of less than 6 months. The decision to initiate treatment is based on these clinical parameters rather than absolute lymphocyte count alone.
Key Factors Influencing Treatment Need
- Age and comorbidities
- Genetic profile, particularly TP53 mutation/17p deletion status
- Presence of symptoms or bulky disease Treatment options have evolved significantly and may include chemoimmunotherapy regimens or targeted therapies such as BTK inhibitors (ibrutinib, acalabrutinib), BCL-2 inhibitors (venetoclax), or PI3K inhibitors. The timing of treatment need varies widely among patients, with some requiring therapy shortly after diagnosis while others may remain stable for many years or even decades without intervention, as noted in 1.
Recent Developments in Treatment
Recent studies, such as 2, highlight the importance of targeted therapies in the management of CLL, with combinations of these agents offering potentially curative therapies with fixed duration. However, the optimal sequencing of targeted therapies remains to be determined, and alternative therapies are needed for patients with BTK and BCL2 inhibitor double-refractory disease. Given the most recent and highest quality evidence from 1, the majority of patients with CLL will require therapy at some point, with treatment decisions guided by clinical parameters and patient-specific factors.