Initiating First-Line (1L) Fixed-Duration (FD) Ibrutinib and Venetoclax (Ibr+Ven) in Patients (Pts) with Chronic Lymphocytic Leukemia (CLL) Improves Overall Survival (OS) Outcomes to Rates Approximating an Age-Matched General European Population
Year: 2024
Type: conference-abstract
Abstract: Introduction: Ibr+Ven is an all-oral, chemotherapy-free, FD treatment option that provides a deep and durable response for treatment-naive (TN) pts with CLL. In the phase 3 GLOW trial, FD Ibr+Ven significantly prolonged OS versus chemoimmunotherapy in pts with TN CLL. With a median follow-up (FU) of up to 5 years, updated results showed a 54-month (mo) OS rate of 84.5% for FD Ibr+Ven compared with 63.7% for chlorambucil plus obinutuzumab, with a hazard ratio (HR) of 0.453 (95% confidence interval [CI], 0.261-0.785). Additionally, in the FD cohort of the phase 2 CAPTIVATE (CAPTIVATE-FD) trial, OS rates at 61.2 mo FU were consistently over 90%, regardless of high-risk features. Here we report OS estimates in pts with CLL treated with 1L FD Ibr+Ven from GLOW and CAPTIVATE-FD versus an age-matched general European population. Aim: OS was assessed for pts with TN CLL receiving FD Ibr+Ven versus a respective age-matched general European population for the following study populations 1) pooled Ibr+Ven-treated pts across GLOW and CAPTIVATE-FD clinical trials; 2) subpopulation of pts aged ≥ 65 years; 3) subpopulation of pts aged < 65 years; 4) subpopulation of pts with mutated IGHV; and 5) subpopulation of pts with unmutated IGHV. Methods: Ibr+Ven data were pooled from 2 clinical trials in pts with TN CLL/small lymphocytic lymphoma: GLOW (NCT03462719; median FU, 55.1 mo) and CAPTIVATE-FD (NCT02910583; median FU, 55.7 mo). Individual trial descriptions and eligibility criteria were reported previously. Post-hoc analysis of IGHV was used for baseline IGHV status for the GLOW study. The OS of pooled pts treated with Ibr+Ven was compared with age-matched simulated survival rates of a general European population using age at randomization. Survival probabilities for the general population by 5-year age intervals from the 2019 World Health Organization life tables were used. To avoid immortal time bias within each age interval, available probabilities were converted to a daily scale. Kaplan-Meier methodology was used for OS analysis, with HRs derived from a Cox proportional-hazards model using trial and simulated data. Results: A total of265 pts (GLOW, n = 106; CAPTIVATE-FD, n = 159) were treated with FD Ibr+Ven in the 1L setting. Median (range) age at randomization was 65 (33-93) years; 135 (50.9%) pts were aged ≥ 65 years. Most (n = 165; 62.3%) pts were male; 248 (93.6%) were White. 145 (54.7%) pts had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 and 107 (40.4%) pts had an ECOG PS of 1. Among pts treated with Ibr+Ven, 156 (58.9%) had unmutated IGHV, 98 (37.0%) had mutated IGHV, and 11 (4.2%) had an unknown IGHV status. Pts with unknown/missing IGHV were excluded in subpopulation analysis based on IGHV status. Median FU time from randomization was 55.7 mo. OS estimates were compared across Ibr+Ven-treated pts and an age-matched European general population; HRs < 1 favored Ibr+Ven. The OS estimate was comparable in the overall population of 265 FD Ibr+Ven-treated pts (HR 0.999; 95% CI, 0.567-1.761; p = 0.998). The estimated OS rates for the overall Ibr+Ven-treated population were 95%, 93%, and 91% at 36, 48, and 60 mo, respectively. The estimated OS was also comparable for 135 Ibr+Ven-treated pts aged ≥ 65 years (HR 0.828; 95% CI, 0.422-1.623; p = 0.582); the estimated 36-, 48-, and 60-mo OS rates were 92%, 90%, and 88%, respectively. For 130 pts aged < 65 years, the estimated OS was similar to their respective age-matched European population (HR 1.636; 95% CI, 0.549-4.875; p = 0.377), with estimated OS rates of 97%, 96%, and 93% at 36, 48, and 60 mo, respectively. The OS estimate for pts with unmutated IGHV was also similar to an age-matched European population (HR 1.182; 95% CI, 0.594-2.351; p = 0.633). Although the HR estimate was numerically favorable for pts with mutated IGHV treated with Ibr+Ven versus an age-matched general European population (HR 0.396; 95% CI, 0.106-1.489; p = 0.171), there were only 3 observed OS events in the FD Ibr+Ven cohort, and the results were not statistically significant. Conclusion: This pooled analysis demonstrates that OS for pts with CLL treated with Ibr+Ven in the 1L setting was comparable to an age-matched general European population, including in the subpopulations of pts aged ≥ 65 years and < 65 years. This study also showed that estimated OS was similar to an age-matched European population, regardless of IGHV mutational status.
Source: Blood
Institutions: Vita-Salute San Raffaele University, Institut universitaire du cancer de Toulouse Oncopole, Universitair Ziekenhuis Leuven, Janssen (Belgium), Universidad Complutense de Madrid, Hospital Universitario Infanta Leonor, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4405040205