Idelalisib or placebo in combination with ...
Type de document :
Article dans une revue scientifique
PMID :
URL permanente :
Titre :
Idelalisib or placebo in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukaemia: interim results from a phase 3, randomised, double-blind, placebo-controlled trial
Auteur(s) :
Zelenetz Andrew, D [Auteur]
Memorial Sloane Kettering Cancer Center [New York]
Barrientos, Jacqueline C [Auteur]
Brown Jennifer, R [Auteur]
Coiffier, Bertrand [Auteur]
Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL]
Delgado, Julio [Auteur]
Barcelona Centre for International Health Research, Hospital Clinic [CRESIB]
Egyed, Miklos [Auteur]
Ghia, Paolo [Auteur]
IRCCS Ospedale San Raffaele [Milan, Italy]
Illes, Arpad [Auteur]
Jurczak, Wojciech [Auteur]
Uniwersytet Jagielloński w Krakowie = Jagiellonian University [UJ]
Marlton, Paula [Auteur]
Montillo, Marco [Auteur]
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
Morschhauser, Franck [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Pristupa Alexander, S [Auteur]
Robak, Tadeusz [Auteur]
Medical University of Łódź [MUL]
Sharman Jeff, P [Auteur]
Simpson, David [Auteur]
Smolej, Lukas [Auteur]
Tausch, Eugen [Auteur]
Adewoye Adeboye, H [Auteur]
Dreiling Lyndah, K [Auteur]
Kim, Yeonhee [Auteur]
Stilgenbauer, Stephan [Auteur]
Hillmen, Peter [Auteur]
St James's University Hospital
Memorial Sloane Kettering Cancer Center [New York]
Barrientos, Jacqueline C [Auteur]
Brown Jennifer, R [Auteur]
Coiffier, Bertrand [Auteur]
Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL]
Delgado, Julio [Auteur]
Barcelona Centre for International Health Research, Hospital Clinic [CRESIB]
Egyed, Miklos [Auteur]
Ghia, Paolo [Auteur]
IRCCS Ospedale San Raffaele [Milan, Italy]
Illes, Arpad [Auteur]
Jurczak, Wojciech [Auteur]
Uniwersytet Jagielloński w Krakowie = Jagiellonian University [UJ]
Marlton, Paula [Auteur]
Montillo, Marco [Auteur]
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
Morschhauser, Franck [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Pristupa Alexander, S [Auteur]
Robak, Tadeusz [Auteur]
Medical University of Łódź [MUL]
Sharman Jeff, P [Auteur]
Simpson, David [Auteur]
Smolej, Lukas [Auteur]
Tausch, Eugen [Auteur]
Adewoye Adeboye, H [Auteur]
Dreiling Lyndah, K [Auteur]
Kim, Yeonhee [Auteur]
Stilgenbauer, Stephan [Auteur]
Hillmen, Peter [Auteur]
St James's University Hospital
Titre de la revue :
The Lancet Oncology
Nom court de la revue :
Lancet Oncol.
Numéro :
18
Pagination :
297-311
Date de publication :
2017-03
ISSN :
1470-2045
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
BACKGROUND: Bendamustine plus rituximab is a standard of care for the management of patients with relapsed or refractory chronic lymphocytic leukaemia. New therapies are needed to improve clinically relevant outcomes in ...
Lire la suite >BACKGROUND: Bendamustine plus rituximab is a standard of care for the management of patients with relapsed or refractory chronic lymphocytic leukaemia. New therapies are needed to improve clinically relevant outcomes in these patients. We assessed the efficacy and safety of adding idelalisib, a first-in-class targeted phosphoinositide-3-kinase δ inhibitor, to bendamustine plus rituximab in this population. METHODS: For this international, multicentre, double-blind, placebo-controlled trial, adult patients (≥18 years) with relapsed or refractory chronic lymphocytic leukaemia requiring treatment who had measurable lymphadenopathy by CT or MRI and disease progression within 36 months since their last previous therapy were enrolled. Patients were randomly assigned (1:1) by a central interactive web response system to receive bendamustine plus rituximab for a maximum of six cycles (bendamustine: 70 mg/m2 intravenously on days 1 and 2 for six 28-day cycles; rituximab: 375 mg/m2 on day 1 of cycle 1, and 500 mg/m2 on day 1 of cycles 2-6) in addition to either twice-daily oral idelalisib (150 mg) or placebo until disease progression or intolerable study drug-related toxicity. Randomisation was stratified by high-risk features (IGHV, del[17p], or TP53 mutation) and refractory versus relapsed disease. The primary endpoint was progression-free survival assessed by an independent review committee in the intention-to-treat population. This trial is ongoing and is registered with ClinicalTrials.gov, number NCT01569295. FINDINGS: Between June 26, 2012, and Aug 21, 2014, 416 patients were enrolled and randomly assigned to the idelalisib (n=207) and placebo (n=209) groups. At a median follow-up of 14 months (IQR 7-18), median progression-free survival was 20·8 months (95% CI 16·6-26·4) in the idelalisib group and 11·1 months (8·9-11·1) in the placebo group (hazard ratio [HR] 0·33, 95% CI 0·25-0·44; p<0·0001). The most frequent grade 3 or worse adverse events in the idelalisib group were neutropenia (124 [60%] of 207 patients) and febrile neutropenia (48 [23%]), whereas in the placebo group they were neutropenia (99 [47%] of 209) and thrombocytopenia (27 [13%]). An increased risk of infection was reported in the idelalisib group compared with the placebo group (grade ≥3 infections and infestations: 80 [39%] of 207 vs 52 [25%] of 209). Serious adverse events, including febrile neutropenia, pneumonia, and pyrexia, were more common in the idelalisib group (140 [68%] of 207 patients) than in the placebo group (92 [44%] of 209). Treatment-emergent adverse events leading to death occurred in 23 (11%) patients in the idelalisib group and 15 (7%) in the placebo group, including six deaths from infections in the idelalisib group and three from infections in the placebo group. INTERPRETATION: Idelalisib in combination with bendamustine plus rituximab improved progression-free survival compared with bendamustine plus rituximab alone in patients with relapsed or refractory chronic lymphocytic leukaemia. However, careful attention needs to be paid to management of serious adverse events and infections associated with this regimen during treatment selection. FUNDING: Gilead Sciences Inc.Lire moins >
Lire la suite >BACKGROUND: Bendamustine plus rituximab is a standard of care for the management of patients with relapsed or refractory chronic lymphocytic leukaemia. New therapies are needed to improve clinically relevant outcomes in these patients. We assessed the efficacy and safety of adding idelalisib, a first-in-class targeted phosphoinositide-3-kinase δ inhibitor, to bendamustine plus rituximab in this population. METHODS: For this international, multicentre, double-blind, placebo-controlled trial, adult patients (≥18 years) with relapsed or refractory chronic lymphocytic leukaemia requiring treatment who had measurable lymphadenopathy by CT or MRI and disease progression within 36 months since their last previous therapy were enrolled. Patients were randomly assigned (1:1) by a central interactive web response system to receive bendamustine plus rituximab for a maximum of six cycles (bendamustine: 70 mg/m2 intravenously on days 1 and 2 for six 28-day cycles; rituximab: 375 mg/m2 on day 1 of cycle 1, and 500 mg/m2 on day 1 of cycles 2-6) in addition to either twice-daily oral idelalisib (150 mg) or placebo until disease progression or intolerable study drug-related toxicity. Randomisation was stratified by high-risk features (IGHV, del[17p], or TP53 mutation) and refractory versus relapsed disease. The primary endpoint was progression-free survival assessed by an independent review committee in the intention-to-treat population. This trial is ongoing and is registered with ClinicalTrials.gov, number NCT01569295. FINDINGS: Between June 26, 2012, and Aug 21, 2014, 416 patients were enrolled and randomly assigned to the idelalisib (n=207) and placebo (n=209) groups. At a median follow-up of 14 months (IQR 7-18), median progression-free survival was 20·8 months (95% CI 16·6-26·4) in the idelalisib group and 11·1 months (8·9-11·1) in the placebo group (hazard ratio [HR] 0·33, 95% CI 0·25-0·44; p<0·0001). The most frequent grade 3 or worse adverse events in the idelalisib group were neutropenia (124 [60%] of 207 patients) and febrile neutropenia (48 [23%]), whereas in the placebo group they were neutropenia (99 [47%] of 209) and thrombocytopenia (27 [13%]). An increased risk of infection was reported in the idelalisib group compared with the placebo group (grade ≥3 infections and infestations: 80 [39%] of 207 vs 52 [25%] of 209). Serious adverse events, including febrile neutropenia, pneumonia, and pyrexia, were more common in the idelalisib group (140 [68%] of 207 patients) than in the placebo group (92 [44%] of 209). Treatment-emergent adverse events leading to death occurred in 23 (11%) patients in the idelalisib group and 15 (7%) in the placebo group, including six deaths from infections in the idelalisib group and three from infections in the placebo group. INTERPRETATION: Idelalisib in combination with bendamustine plus rituximab improved progression-free survival compared with bendamustine plus rituximab alone in patients with relapsed or refractory chronic lymphocytic leukaemia. However, careful attention needs to be paid to management of serious adverse events and infections associated with this regimen during treatment selection. FUNDING: Gilead Sciences Inc.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
CHU Lille
CHU Lille
Collections :
Équipe(s) de recherche :
Innovation/évaluation des médicaments injectables
Date de dépôt :
2019-02-26T17:07:16Z
2022-02-02T10:43:47Z
2022-02-02T10:43:47Z
Fichiers
- nihms889304.pdf
- Version éditeur
- Accès libre
- Accéder au document