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

1st Faculty of Medicine Charles University Prague and General University Hospital Prague Prague Czech Republic

3rd Medical Department at the Paracelsus Medical University Salzburg Salzburg Austria; Salzburg Cancer Research Institute Salzburg Austria

3rd Medical Department for Hematology and Oncology Hanusch Krankenhaus der Wiener Gebietskrankenkasse Vienna Austria

4th Department of Internal Medicine Hematology University Hospital and Charles University Prague Faculty of Medicine in Hradec Králové Hradec Králové Czech Republic

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

Clinic of Haematology Regional Institute of Oncology Iasi Iasi Romania

Clinic of Hematology and Transfusiology Slovak Medical University University Hospital Bratislava Slovakia

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

University Hospital Krems Karl Landsteiner Private University of Health Sciences Department of Internal Medicine 2 Krems Austria

Citace poskytuje Crossref.org

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ClinicalTrials.gov
NCT01118234