A pooled analysis of data from the phase 3 GLOW trial and the fixed-duration cohort of the phase 2 CAPTIVATE study indicates that first-line treatment with ibrutinib (Imbruvica) plus venetoclax (Venclexta) results in overall survival (OS) outcomes comparable to those of an age-matched general European population in patients with treatment-naive chronic lymphocytic leukemia (CLL). The findings, presented at the 2024 ASH Annual Meeting, suggest a significant improvement in survival for CLL patients treated with this combination therapy.
The analysis included 265 patients (GLOW, n = 106; CAPTIVATE-FD, n = 159) who received fixed-duration ibrutinib plus venetoclax. The primary objective was to compare the OS rates of these patients with those of an age-matched general European population. The study considered various age groups and immunoglobulin gene mutation status to provide a comprehensive assessment.
Survival Outcomes
The pooled analysis revealed that the estimated 36-, 48-, and 60-month OS rates in the overall study population were 95%, 93%, and 91%, respectively. These rates were statistically comparable with those observed in the general population (HR, 0.999; 95% CI, 0.567-1.761; P = .998). According to Dr. Paolo Ghia, MD, PhD, from Università Vita-Salute San Raffaele, "The OS estimates in this population were similar to [that of] the age-matched general European population, and that was true for both young and elderly patients."
Impact on Older Patients
Notably, the combination therapy also demonstrated similar benefits in older patients. Among patients aged 65 years or older (n = 135), the estimated 36-, 48-, and 60-month OS rates were 92%, 90%, and 88%, respectively, which were comparable with those for the age-matched general population (HR, 0.828; 95% CI, 0.422-1.623; P = .582).
Implications for CLL Treatment
These findings underscore the potential of fixed-duration ibrutinib plus venetoclax as a first-line treatment option for CLL, offering the possibility of normalized survival outcomes. The 46-month follow-up of the GLOW trial previously showed that patients receiving this combination had improved OS outcomes compared to those treated with chlorambucil plus obinutuzumab (HR, 0.487; P = .021). Earlier results from CAPTIVATE-FD, with a median follow-up of 61.2 months, reported an OS rate of 96% with ibrutinib plus venetoclax.
