The objective of this study was to describe treatment burden among patients aged ≥75 years diagnosed with chronic lymphocytic leukemia (CLL), defined as the likelihood of receiving subsequent lines of therapy over time.
A retrospective observational cohort study was conducted using the U.S. Flatiron Health electronic health record–derived, deidentified database. Patients aged ≥75 years at diagnosis who initiated first–line CLL therapy between January 2011 and October 2025 were included. Patients were followed from first–line treatment initiation until the earliest of second–line initiation, death, end of follow–up, or study end. The primary outcome was the cumulative probability of receiving next treatment, with death treated as a competing risk using cumulative incidence functions. Secondary analyses described first–line treatment patterns by time period and age group and assessed frequencies of Richter transformation during follow–up.
A total of 3,234 patients were included, with a median age of 79 years at diagnosis. Overall, 60% were male and 73% were non–Hispanic White. At baseline, 27% of patients had an ECOG performance status of 0 and 33% had ECOG performance status of 1. Del(17p)/TP53 mutation was reported in 13% of patients, and unmutated IGHV was reported in 14%. Median time from diagnosis to first–line therapy initiation was 10.4 months (IQR, 1.7-29.5). Most patients were aged 75–79 years at diagnosis (59%), followed by 80–84 years (38%) and ≥85 years (4%). Overall median follow-up was 24.7 months (IQR, 8.9-48.1) with decreasing follow-up observed across increasing age strata (median 35.8 months in 75-79 years, 16.2 months in 80-84 years, and 1.7 months in ≥85 years).
The cumulative probability of receiving second–line therapy increased continuously over time, reaching 12.4% (95% CI, 11.3%-13.6%) at 6 months, 28.5% (95% CI, 26.8%-30.1%) at 24 months, 37.9% (95% CI, 36.1%-39.8%) at 48 months, and 46.5% (95% CI, 44.2%-48.6%) at 96 months, without evidence of plateau. The likelihood of receiving 2L was higher in patients aged 75-79 years with 53.3% (95% CI, 50.3%-56.1%) of patients receiving 2L by the end of follow-up compared with 34.4% (95% CI, 31.4%-37.4%) in patients aged ≥80 years. Bruton tyrosine kinase inhibitor monotherapy was the most common first–line treatment since 2014 overall and across age groups. Richter transformation occurred in 1.7% of patients, and 52.3% died during follow–up, with a median age at death of 85 years.
