%0 Journal Article
%T Overall survival of patients with CLL treated with ibrutinib in the first line compared to second-line ibrutinib after chemotherapy/chemoimmunotherapy.
%A Robak T
%A Doubek M
%A Ferrant E
%A Diels J
%A Andersone L
%A Wilbertz S
%A Healy NC
%A Neumayr L
%A van Sanden S
%J Curr Med Res Opin
%V 40
%N 8
%D 2024 Aug 1
%M 38885086
%F 2.705
%R 10.1080/03007995.2024.2368175
%X <B>UNASSIGNED: </B>To evaluate the overall survival (OS) of patients with chronic lymphocytic leukemia (CLL) receiving either ibrutinib monotherapy as a first-line (1L) treatment or chemotherapy/chemoimmunotherapy-based (CT/CIT) regimens in 1L followed by ibrutinib in the second line (1L CT/CIT-2L ibrutinib) after disease progression by emulating a randomized trial comparing both treatment sequences.<BR><B>UNASSIGNED: </B>Patient-level data from the RESONATE-2 trial (NCT01722487) and real-world PHEDRA databases were analyzed. Three scenarios were considered using the following data sources: (1) RESONATE-2, (2) combined RESONATE-2/PHEDRA, (3) combined RESONATE-2/PHEDRA for 1L ibrutinib and PHEDRA for 1L CT/CIT-2L ibrutinib. Propensity score-based weights and inverse probability of censoring weighting were used to adjust for baseline (Scenarios 2 and 3) and time-dependent confounding (all scenarios), and to address potential biases. A weighted Cox proportional hazards model was used to estimate the OS hazard ratio (HR) and 95% confidence interval (CI) for 1L ibrutinib versus 1L CT/CIT-2L ibrutinib.<BR><B>UNASSIGNED: </B>Results from Scenario 1 showed a significantly lower risk of death with 1L ibrutinib compared with 1L chlorambucil followed by 2L ibrutinib (HR 0.35 [95% CI 0.20-0.62]). Results from Scenarios 2 and 3 demonstrated a reduced risk of death with 1L ibrutinib compared with 1L CT/CIT-2L ibrutinib (HR 0.35 [0.21-0.61] and 0.64 [0.39-1.04], respectively).<BR><B>UNASSIGNED: </B>The analyses consistently showed a reduced risk of death when ibrutinib was used as a 1L treatment in CLL compared with delaying its use until 2L after CT/CIT regimens, which suggests that initiating ibrutinib in 1L is advantageous for improving survival outcomes.