Real-World Analysis Shows Substantial Treatment Burden in Older Patients With CLL/SLL

Findings from a retrospective cohort study revealed the substantial treatment burden that remains among patients at least 75 years of age with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to data presented at the 2026 EHA Congress.¹

Using a competing-risk analysis that accounted for death, the cumulative probability of receiving second-line therapy increased throughout the follow-up period and did not plateau. Among patients 75 to 79 years of age, 53.3% (95% CI, 50.3%-56.1%) received second-line treatment by the end of follow-up, compared with 34.4% (95% CI, 31.4%-37.4%) of those 80 years of age or older. A sensitivity analysis restricted to patients who started first-line therapy between 2011 and 2022 yielded similar results, with a cumulative incidence of 45.5% (95% CI, 43.3%-47.8%) at 96 months.

“These findings underscore the importance of frontline choices that account for longitudinal treatment sequencing, particularly in older patients,” lead study author Daniel A. Ermann, MD, and coauthors wrote in a poster.

Ermann is an associate professor in the Division of Hematology/Hematologic Malignancies at the University of Utah Health in Salt Lake City.

How was the CLL/SLL treatment burden analysis designed?

The retrospective, observational study used the Flatiron Health US nationwide de-identified electronic health record–derived database. Eligible patients were 75 years of age or older at CLL/SLL diagnosis; were diagnosed between January 1, 2011, and October 31, 2025; had received at least 1 line of therapy; and did not have missing treatment information. Patients were followed from the start of first-line treatment (index date) until the earliest of next treatment/second-line start, end of follow-up, death, or study end. The primary outcome was the cumulative probability of starting next treatment, with death modeled as a competing risk.

A total of 3234 patients were included. The median age was 79 years at diagnosis, 60% of patients were male, and 73% of patients were non-Hispanic White. Among all patients, at diagnosis, 59% were 75 to 79 years of age, 38% were 80 to 84 years of age, and 4% were 85 years of age or older. The overall median follow-up was 24.7 months (interquartile range, 8.9-48.1), with decreasing follow-up observed across increasing age strata: 35.8 months in patients 75 to 79 years of age, 16.2 months in those 80 to 84 years of age, and 1.7 months in those 85 years of age or older.

How did likelihood of next treatment differ by age and biomarker status in older patients with CLL/SLL?

Beyond the age group difference, the likelihood of receiving second-line therapy was consistently higher among patients who were not tested for 17p deletions (del[17p]) and/or TP53 mutations. At 96 months, the cumulative incidence of next treatment was 42.0% in patients with del(17p)/TP53-mutated disease, 46.8% in those without TP53-mutated disease, and 48.4% in patients who were not tested. Results were similar across IGHV mutation status until 60 months or later.

These patterns align with prior real-world and trial data examining front-line outcomes in this population. A separate real-world analysis presented at the 2026 ASCO Annual Meeting showed that zanubrutinib (Brukinsa) was associated with longer time to next treatment and improved overall survival compared with acalabrutinib (Calquence) in patients with treatment-naive CLL,² and long-term follow-up from the phase 3 SEQUOIA trial(NCT03336333)presented at the 2026 EHA Congress demonstrated durable progression-free survival with zanubrutinib in older patients with treatment-naive CLL/SLL.³

What was the most common frontline treatment among older patients with CLL/SLL, and what are the study’s limitations?

BTK inhibitor monotherapy was the most common first-line treatment since 2014, both overall and across age groups; prior to 2014, rituximab (Rituxan) monotherapy predominated. During follow-up, 1.7% of patients experienced Richter transformation, and 52.3% of patients died (median age at death, 85 years).

The investigators noted that the treatment burden was likely underestimated, as rates of subsequent therapy are expected to increase with longer follow-up, a limitation compounded by the shorter follow-up observed in the oldest age strata. They added that identifying and predicting which patients will avoid second-line treatment remains challenging.

References

1. Ermann DA, Alsouqi A, Wang X, et al. Treatment burden among patients aged 75 years or older with chronic lymphocytic leukemia and small lymphocytic lymphoma. Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract PF605.
2. Ryan C. Zanubrutinib yields real-world TTNT and OS benefits vs acalabrutinib in treatment-naive CLL. OncLive.com. June 11, 2026. Accessed June 17, 2026. https://www.onclive.com/view/zanubrutinib-yields-real-world-ttnt-and-os-benefits-vs-acalabrutinib-in-treatment-naive-cll
3. OncLive Staff .Zanubrutinib displays durable long-term efficacy, safety in older treatment-naive CLL/SLL. OncLive.com. June 15, 2026. Accessed June 17, 2026. https://www.onclive.com/view/zanubrutinib-displays-durable-long-term-efficacy-safety-in-older-treatment-naive-cll-sll