Venetoclax Effective in Older Patients With CLL

Venetoclax (Venclexta; Abbvie, Genentech) has a high response rate in octogenarians with chronic lymphocytic leukemia (CLL), but clinicians should expect treatment-management challenges such as temporary stops.¹

Those are among the key findings of a new retrospective study that examined the safety and efficacy of the BCL-2 inhibitor in older patients. The report was published in Blood Advances.

Venetoclax showed “remarkable efficacy” in older patients, with an response rate of 91% in the octogenarian group—similar to what has been reported in younger cohorts. | Image credit: sovova - stock.adobe.com

Most people diagnosed with CLL are aged 65 years or older, a fact related in part to the indolent course of the disease, explained corresponding author Livio Trentin, MD, of Italy’s University of Padova, and colleagues. According to the National Institutes of Health, the median age of a newly diagnosed patient with CLL is 70 years.² In addition, one-quarter of patients will be diagnosed between the ages of 75 and 84, and 11.3% of patients are older than age 84 when diagnosed.

Yet, despite the high prevalence of elderly patients within the broader CLL patient population, Trentin and colleagues said people over the age of 80 are often excluded from clinical trials and are generally understudied.¹ Therefore, more evidence is needed to help clinicians make better-informed choices.

The new study included 120 patients over the age of 80 who were treated for CLL at one of 23 Italian medical centers between 2014 and 2023. The median age at the start of therapy was 81 years. The patients tended to have significant comorbidities; more than half of the patients (54%) had Cumulative Illness Rating Scale scores greater than 6. Fifty-three percent of patients had impaired renal function, more than three-quarters of patients were considered to be at intermediate or high risk of tumor lysis syndrome, and 28% of patients had a TP53 mutation and/or del(17p). Most patients (83%) had relapsed or refractory disease, with a median of 2 lines of prior therapy.

Half of the participants received venetoclax as monotherapy (50%), 45 patients received venetoclax in combination with rituximab (Rituxan; Genentech, Biogen), and 17 patients received venetoclax in combination with obinutuzumab (Gazyva; Genentech).

Trentin and colleagues said the therapy showed “remarkable efficacy” in this patient group. The overall response rate of 91% in the octogenarian group was similar to what has been reported in younger cohorts. The same is true of the complete response rate of 44% and progression-free survival of 44 months.

In terms of safety, the investigators found neutropenia (37%) was common, as were infections of grade 3 or higher (22%).

The investigators said patient management was an important factor among the cohort. One-third (32%) of patients needed a ramp-up time for venetoclax that exceeded 5 weeks. Only 78% of patients eventually reached the full 400-mg dose of the therapy. And, the authors said, 43% of patients needed temporary interruptions of at least 7 days.

Trentin and colleagues then compared their findings to data from a similar population of patients treated with Bruton tyrosine kinase inhibitors (BTKis).

“We found that these two treatments were comparable in terms of overall efficacy, barring a higher rate of complete responses with venetoclax,” they wrote.

However, they added that the safety profiles were somewhat different. Twenty-six percent of patients treated with BTKIs experienced cardiovascular toxicities, compared with just 4% among the venetoclax-treated population. However, 82% of participants in the venetoclax cohort experienced infectious events, compared with just 49% of patients who received a BTKi. Yet, the investigators added that rates of grade 3 and 4 infections, specifically, were similar between the 2 groups.

Trentin and colleagues said the comparison between venetoclax and BTKIs should be interpreted with some caution, since there was a greater proportion of patients with high-risk genetic lesions in the latter cohort. The retrospective nature of the study and the heterogeneity of the patient cohorts were also limiting factors in their research.

“Nevertheless, our study represents a key step towards the achievement of a better standard of care for elderly patients requiring treatment for CLL, providing real-world evidence for the usage of venetoclax-based combinations in this patient population, and improving on some previously published data on the usage of BTKIs,” they wrote.

References

1. Serafin A, Cellini A, Martino EA, et al. Venetoclax-based regimens in octogenarian CLL patients: efficacy, safety, and comparison to BTKi in a multicenter cohort. Blood Adv. Published online April 16, 2025. doi:10.1182/bloodadvances.2025015818

2. SEER cancer stat facts — chronic lymphocytic leukemia (CLL). Surveillance, Epidemiology, and End Results Program. Accessed June 10, 2025. https://seer.cancer.gov/statfacts/html/clyl.html