Dr Ghia on Fixed-Duration Ibrutinib Plus Venetoclax in First-Line CLL

“Additional information, together with information that we obtained from [earlier] studies, show the long-term efficacy and durability of the progression-free survival, which was very long, [including in] patients with high-risk features.”

Paolo Ghia, MD, PhD, full professor of medical oncology at Università Vita-Salute San Raffaele, and director of the Strategic Research Program on CLL at IRCCS Ospedale San Raffaele, discussed updated findings from a pooled analysis of the phase 3 GLOW trial (NCT03462719) and the fixed-duration cohort of the phase 2 CAPTIVATE study (NCT02910583), which evaluated first-line, fixed-duration ibrutinib (Imbruvica) plus venetoclax (Venclexta) in patients with treatment-naive chronic lymphocytic leukemia (CLL).

Findings presented at the 2024 ASH Annual Meeting demonstrated that fixed-duration ibrutinib plus venetoclax was associated with overall survival (OS) outcomes that approximated those of an age-matched general European population. The pooled analysis included 265 patients treated with the combination (GLOW, n = 106; CAPTIVATE, n = 159) and assessed OS rates at 36, 48, and 60 months.

In the overall population, estimated OS rates were 95% at 36 months, 93% at 48 months, and 91% at 60 months. These values were consistent with those observed in the general European population, and no significant difference in OS was observed (HR, 0.999; 95% CI, 0.567-1.761; P = .998). The analysis further stratified outcomes by age group. Among patients 65 years of age and older (n = 135), estimated OS rates were 92%, 90%, and 88% at 36, 48, and 60 months, respectively (HR, 0.828; 95% CI, 0.422-1.623; P = .582). For patients younger than 65 years (n = 130), corresponding OS rates were 97%, 96%, and 93% (HR, 1.636; 95% CI, 0.549-4.875; P = .377).

Ghia noted that the survival benefit with ibrutinib plus venetoclax was observed regardless of IGHV mutation status. Both IGHV-mutated and -unmutated subgroups experienced comparable OS trajectories, supporting the broad applicability of this fixed-duration regimen across risk groups.