Ibrutinib versus previous standard of care: an adjusted comparison in patients with relapsed/refractory chronic lymphocytic leukaemia

Abstract

This study explored the relative efficacy of ibrutinib versus previous standard-of-care treatments in relapsed/refractory patients with chronic lymphocytic leukaemia (CLL), using multivariate regression modelling to adjust for baseline prognostic factors. Individual patient data were collected from an observational Stockholm cohort of consecutive patients (n = 144) diagnosed with CLL between 2002 and 2013 who had received at least second-line treatment. Data were compared with results of the RESONATE clinical trial. A multivariate Cox proportional hazards regression model was used which estimated the hazard ratio (HR) of ibrutinib versus previous standard of care. The adjusted HR of ibrutinib versus the previous standard-of-care cohort was 0.15 (p < 0.0001) for progression-free survival (PFS) and 0.36 (p < 0.0001) for overall survival (OS). A similar difference was observed also when patients treated late in the period (2012-) were compared separately. Multivariate analysis showed that later line of therapy, male gender, older age and poor performance status were significant independent risk factors for worse PFS and OS. Our results suggest that PFS and OS with ibrutinib in the RESONATE study were significantly longer than with previous standard-of-care regimens used in second or later lines in routine healthcare. The approach used, which must be interpreted with caution, compares patient-level data from a clinical trial with outcomes observed in a daily clinical practice and may complement results from randomised trials or provide preliminary wider comparative information until phase 3 data exist.

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

“…Other published analyses support the current findings, showing the clinical benefits of ibrutinib outside of RCTs [31]. Using similar methodology to the current study, PLD were collected from an observational cohort of R/R patients ( n = 144) diagnosed with CLL between 2002 and 2013 in Sweden, and the ibrutinib arm of RESONATE™.…”

Mammalian Plakins, Giant Cytolinkers: Versatile Biological Functions and Roles in Cancer

“…More recently, Quick, by using the Research Collaboratory for Structural Bioinformatics (RCSB) protein data bank, has identified several anticancer drugs that interact with BPAG1, MACF1, and plectin [ 143 ]. Ibrutinib is one common ligand for both BPAG1 and MACF1, and is used clinically for the treatment of lymphoma and leukemia [ 144 , 145 ]. PP121, showing antitumorigenic effects on esophageal cancer and anaplastic thyroid carcinoma by perturbing PI3K and mammalian target of rapamycin (mTOR) kinase activities [ 146 , 147 ], is identified as an MACF1 ligand.…”

Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib: a GIMEMA, ERIC and UK CLL FORUM study

“…In another analysis including R/R CLL in second and subsequent lines of treatment, 29 an OS advantage was noted when comparing ibrutinib (with or without BR) and BR alone. 30 In other studies arriving at the same conclusion, 31 , 32 chemotherapy +/− anti CD20 regimens used in a real-world setting were compared with ibrutinib data of the clinical trials Resonate and Helios. However, there is now evidence that adherence to treatment with ibrutinib in the real-world population did not reflect the data obtained in clinical trials, 22 , 33 possibly due to the heterogeneity of the patient populations or to a more limited experience of physicians in managing side effects occurring on treatment.…”