Single-agent ibrutinib in RESONATE-2 (TM) and RESONATE (TM) versus treatments in the real-world PHEDRA databases for patients with chronic lymphocytic leukemia

Authors	SALLES Gilles BACHY Emmanuel SMOLEJ Lukáš SIMKOVIC Martin BASEGGIO Lucile PANOVSKÁ Anna BESSON Herve HEALY Nollaig GARSIDE Jamie IRAQI Wafae DIELS Joris PICK-LAUER Corinna SPACEK Martin URBANOVA Renata LYSAK Daniel HERMANS Ruben LUNDBOM Jessica CALLET-BAUCHU Evelyne DOUBEK Michael
Year of publication	2019
Type	Article in Periodical
Magazine / Source	Annals of hematology
MU Faculty or unit	Faculty of Medicine
Citation
Web	http://dx.doi.org/10.1007/s00277-019-03830-8
Doi	http://dx.doi.org/10.1007/s00277-019-03830-8
Keywords	Ibrutinib; Chronic lymphocytic leukemia; Real-world evidence; Randomized controlled trial; Progression-free survival; Overall survival
Description	After analyzing treatment patterns in chronic lymphocytic leukemia (CLL) (objective 1), we investigated the relative effectiveness of ibrutinib versus other commonly used treatments (objective 2) in patients with treatment-naive and relapsed/refractory CLL, comparing patient-level data from two randomized registration trials with two real-world databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using a multivariate Cox proportional hazards model, adjusted for differences in baseline characteristics. Rituximab-containing regimens were often prescribed in clinical practice. The most frequently prescribed regimens were fludarabine + cyclophosphamide + rituximab (FCR, 29.3%), bendamustine + rituximab (BR, 17.7%), and other rituximab-containing regimens (22.0%) in the treatment-naive setting (n = 604), other non-FCR/BR rituximab-containing regimens (38.7%) and non-rituximab-containing regimens (28.5%) in the relapsed/refractory setting (n = 945). Adjusted HRs (95% CI) for progression-free survival (PFS) and overall survival (OS), respectively, with ibrutinib versus real-world regimens were 0.23 (0.14-0.37; p < 0.0001) and 0.40 (0.22-0.76; p = 0.0048) in the treatment-naive setting, and 0.21 (0.16-0.27; p < 0.0001) and 0.29 (0.21-0.41; p < 0.0001) in the relapsed/refractory setting. When comparing real-world use of ibrutinib (n = 53) versus other real-world regimens in relapsed/refractory CLL (objective 3), adjusted HRs (95% CI) were 0.37 (0.22-0.63; p = 0.0003) for PFS and 0.53 (0.27-1.03; p < 0.0624) for OS. This adjusted analysis, based on nonrandomized patient data, suggests ibrutinib to be more effective than other commonly used regimens for CLL.