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Rituximab maintenance versus observation alone in patients with chronic lymphocytic leukaemia who respond to first-line or second-line rituximab-containing chemoimmunotherapy: final results of the AGMT CLL-8a Mabtenance randomised trial
R. Greil, P. Obrtlíková, L. Smolej, T. Kozák, M. Steurer, J. Andel, S. Burgstaller, E. Mikušková, L. Gercheva, T. Nösslinger, T. Papajík, M. Ladická, M. Girschikofsky, M. Hrubiško, U. Jäger, M. Fridrik, M. Pecherstorfer, E. Králiková, C....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu klinické zkoušky, fáze III, srovnávací studie, časopisecké články, multicentrická studie, randomizované kontrolované studie
- MeSH
- bendamustin hydrochlorid aplikace a dávkování MeSH
- chronická lymfatická leukemie farmakoterapie patologie patofyziologie MeSH
- cyklofosfamid aplikace a dávkování MeSH
- dospělí MeSH
- imunoterapie * MeSH
- indukce remise MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- protokoly antitumorózní kombinované chemoterapie aplikace a dávkování terapeutické užití MeSH
- rituximab aplikace a dávkování MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- vidarabin aplikace a dávkování analogy a deriváty MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
BACKGROUND: In many patients with chronic lymphocytic leukaemia requiring treatment, induction therapy with rituximab plus chemotherapy improves outcomes compared with chemotherapy alone. In this study we aimed to investigate the potential of rituximab maintenance therapy to prolong disease control in patients who respond to rituximab-containing induction regimens. METHODS: In this randomised, international, multicentre, open-label, phase 3 clinical trial, we enrolled patients who had achieved a complete response (CR), CR with incomplete bone marrow recovery (CRi), or partial response (PR) to first-line or second-line rituximab-containing chemoimmunotherapy and randomly assigned them in a 1:1 ratio (central block randomisation in the electronic case report form system) to either intravenous rituximab 375 mg/m(2) every 3 months, or observation alone, for 2 years. Stratification was by country, line of treatment, type of chemotherapy added to the rituximab backbone, and degree of remission following induction. The primary endpoint was progression-free survival. Efficacy analysis was done in the intention-to-treat population. This is the final, event-triggered analysis. Final analysis was triggered by the occurrence of 92 events. This trial is registered with ClinicalTrials.gov, number NCT01118234. FINDINGS: Between April 1, 2010, and Dec 23, 2013, 134 patients were randomised to rituximab and 129 to observation alone. Median observation times were 33·4 months (IQR 25·7-42·8) for the rituximab group and 34·0 months (25·4-41·9) for the observation group. Progression-free survival was significantly longer in the rituximab maintenance group (47·0 months, IQR 28·5-incalculable) than with observation alone (35·5 months, 95% CI 25·7-46·3; hazard ratio [HR] 0·50, 95% CI 0·33-0·75, p=0·00077). The incidence of grade 3-4 haematological toxicities other than neutropenia was similar in the two treatment groups. Grade 3-4 neutropenia occurred in 28 (21%) patients in the rituximab group and 14 (11%) patients in the observation group. Apart from neutropenia, the most common grade 3-4 adverse events were upper (five vs one [1%] patient in the observation group) and lower (three [2%] vs one [1%]) respiratory tract infection, pneumonia (nine [7%] vs two [2%]), thrombopenia (four [3%] vs four [3%]), neoplasms (five [4%] vs four [3%]), and eye disorders (four [3%] vs two [2%]). The overall incidence of infections of all grades was higher among rituximab recipients (88 [66%] vs 65 [50%]). INTERPRETATION: Rituximab maintenance therapy prolongs progression-free survival in patients achieving at least a PR to induction with rituximab plus chemotherapy, and the treatment is well tolerated overall. Although it is associated with an increase in infections, there is no excess in infection mortality, suggesting that remission maintenance with rituximab is an effective and safe option in the management of chronic lymphocytic leukaemia in early treatment phases. FUNDING: Arbeitsgemeinschaft Medikamentöse Tumortherapie gemeinnützige GmbH (AGMT), Roche.
1 Interne Abteilung Elisabethinen Krankenhaus Linz Austria
3rd Medical Department at the Paracelsus Medical University Salzburg Salzburg Austria
Abteilung für Innere Medizin 3 Landeskrankenhaus Steyr Austria
Abteilung für Innere Medizin 4 Klinikum Wels Grieskirchen GmbH Austria
Assign Data Management and Biostatistics GmbH Innsbruck Austria
Cancer Cluster Salzburg Salzburg Austria
Clinic of Haematology Regional Institute of Oncology Iasi Iasi Romania
Clinic of Hematology UMHAT St George and Medical University Plovdiv Bulgaria
Clinic of Hematology University Hospital St Marina Varna Bulgaria
Clinic of Medical Hematology Military Medical Academy Sofia Bulgaria
Department of Clinical Hematology FNsP J A Reimana Prešov Slovakia
Department of Clinical Oncology 1 National Cancer Institute Bratislava Slovakia
Department of Hemato oncology University Hospital Olomouc Czech Republic
Department of Hematology and Transfusion University Hospital Martin Martin Slovakia
Department of Hematology FNsP F D Roosevelta Banská Bystrica Slovakia
Department of Hematooncology 2 National Cancer Institute Bratislava Slovakia
Department of Internal Medicine 3 Kepler Universitätsklinikum GmbH Med Campus 3 Linz Austria
Department of Internal Medicine 5 Medical University Innsbruck Austria
Department of Internal Medicine Hematology Univ Hospital Kralovske Vinohrady Prague Czech Republic
Department of Medicine 1 Division of Hematology and Hemostaeology Medical University Vienna Austria
Hematological Clinic NSHATHD Sofia Bulgaria
Innere Medizin 1 Krankenhaus der Barmherzigen Schwestern Linz Linz Austria
Innere Medizin 2 Bezirkskrankenhaus Kufstein Austria
Innere Medizin Landeskrankenhaus Hall Austria
Salzburg Cancer Research Institute Salzburg Austria
University Hospital Faculty of Medicine and CEITEC Brno Czech Republic
Citace poskytuje Crossref.org
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- $a BACKGROUND: In many patients with chronic lymphocytic leukaemia requiring treatment, induction therapy with rituximab plus chemotherapy improves outcomes compared with chemotherapy alone. In this study we aimed to investigate the potential of rituximab maintenance therapy to prolong disease control in patients who respond to rituximab-containing induction regimens. METHODS: In this randomised, international, multicentre, open-label, phase 3 clinical trial, we enrolled patients who had achieved a complete response (CR), CR with incomplete bone marrow recovery (CRi), or partial response (PR) to first-line or second-line rituximab-containing chemoimmunotherapy and randomly assigned them in a 1:1 ratio (central block randomisation in the electronic case report form system) to either intravenous rituximab 375 mg/m(2) every 3 months, or observation alone, for 2 years. Stratification was by country, line of treatment, type of chemotherapy added to the rituximab backbone, and degree of remission following induction. The primary endpoint was progression-free survival. Efficacy analysis was done in the intention-to-treat population. This is the final, event-triggered analysis. Final analysis was triggered by the occurrence of 92 events. This trial is registered with ClinicalTrials.gov, number NCT01118234. FINDINGS: Between April 1, 2010, and Dec 23, 2013, 134 patients were randomised to rituximab and 129 to observation alone. Median observation times were 33·4 months (IQR 25·7-42·8) for the rituximab group and 34·0 months (25·4-41·9) for the observation group. Progression-free survival was significantly longer in the rituximab maintenance group (47·0 months, IQR 28·5-incalculable) than with observation alone (35·5 months, 95% CI 25·7-46·3; hazard ratio [HR] 0·50, 95% CI 0·33-0·75, p=0·00077). The incidence of grade 3-4 haematological toxicities other than neutropenia was similar in the two treatment groups. Grade 3-4 neutropenia occurred in 28 (21%) patients in the rituximab group and 14 (11%) patients in the observation group. Apart from neutropenia, the most common grade 3-4 adverse events were upper (five vs one [1%] patient in the observation group) and lower (three [2%] vs one [1%]) respiratory tract infection, pneumonia (nine [7%] vs two [2%]), thrombopenia (four [3%] vs four [3%]), neoplasms (five [4%] vs four [3%]), and eye disorders (four [3%] vs two [2%]). The overall incidence of infections of all grades was higher among rituximab recipients (88 [66%] vs 65 [50%]). INTERPRETATION: Rituximab maintenance therapy prolongs progression-free survival in patients achieving at least a PR to induction with rituximab plus chemotherapy, and the treatment is well tolerated overall. Although it is associated with an increase in infections, there is no excess in infection mortality, suggesting that remission maintenance with rituximab is an effective and safe option in the management of chronic lymphocytic leukaemia in early treatment phases. FUNDING: Arbeitsgemeinschaft Medikamentöse Tumortherapie gemeinnützige GmbH (AGMT), Roche.
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