Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): A phase 3, randomised controlled trial

Gilles Salles, John Francis Seymour, Fritz Offner, Armando López-Guillermo, David Belada, Luc Xerri, Pierre Feugier, Réda Bouabdallah, John Vincent Catalano, Pauline Brice, Dolores Caballero, Corinne Haioun, Lars Moller Pedersen, Alain Delmer, David Simpson, Sirpa Leppa, Pierre Soubeyran, Anton Hagenbeek, Rene Olivier Casasnovas, Tanin IntragumtornchaiChristophe Fermé, Maria Gomes Da Silva, Catherine Sebban, Andrew Lister, Jane A. Estell, Gustavo Milone, Anne Sonet, Myriam Mendila, Bertrand B Coiffier, Hervé Tilly

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Abstract

Patients with follicular lymphoma can have long survival times, but disease progression typically occurs 3-5 years after initial treatment. We assessed the potential benefit of 2 years of rituximab maintenance after first-line treatment in patients with follicular lymphoma receiving a rituximab plus chemotherapy regimen. The randomised, open-label PRIMA study was undertaken in 223 centres in 25 countries. 1217 patients with previously untreated follicular lymphoma needing systemic therapy received one of three non-randomised immunochemotherapy induction regimens used in routine practice. 1019 patients achieving a complete or partial response were then randomly assigned to receive 2 years of rituximab maintenance therapy (375 mg/m2 every 8 weeks) or observation. Treatment was assigned equally by centralised block randomisation, stratified by induction regimen, response, region, and centre. Neither the participants nor those giving the interventions, assessing outcomes, and analysing data were masked to group assignments. The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00140582. 505 patients were assigned to rituximab maintenance and 513 to observation (one patient died during randomisation). With a median follow-up of 36 months (IQR 30-42), PFS was 74·9 (95 CI 70·9-78·9) in the rituximab maintenance group (130 patients progressed) and 57·6 (53·2-62·0) in the observation group (218 progressed; hazard ratio [HR] 0·55, 95 CI 0·44-0·68, p<0·0001). 2 years after randomisation, 361 patients (71·5) in the rituximab maintenance group were in complete or unconfirmed complete response versus 268 (52·2) in the observation group (p=0·0001). Overall survival did not differ significantly between groups (HR 0·87, 95 CI 0·51-1·47). Grade 3 and 4 adverse events were recorded in 121 patients (24) in the rituximab maintenance group and 84 (17) in the observation group (risk ratio 1·46, 95 CI 1·14-1·87; p=0·0026). Infections (grades 2-4) were the most common adverse event, occurring in 197 (39) and 123 (24) patients, respectively (risk ratio 1·62, 95 CI 1·35-1·96; p<0·0001). 2 years of rituximab maintenance therapy after immunochemotherapy as first-line treatment for follicular lymphoma significantly improves PFS. Groupe d'Etude des Lymphomes de l'Adulte (GELA) and F Hoffmann-La Roche.

Original languageEnglish
Pages (from-to)42-51
Number of pages10
JournalThe Lancet
Volume377
Issue number9759
DOIs
Publication statusPublished - 1 Jan 2011
Externally publishedYes

Cite this

Salles, G., Seymour, J. F., Offner, F., López-Guillermo, A., Belada, D., Xerri, L., Feugier, P., Bouabdallah, R., Catalano, J. V., Brice, P., Caballero, D., Haioun, C., Pedersen, L. M., Delmer, A., Simpson, D., Leppa, S., Soubeyran, P., Hagenbeek, A., Casasnovas, R. O., ... Tilly, H. (2011). Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): A phase 3, randomised controlled trial. The Lancet, 377(9759), 42-51. https://doi.org/10.1016/S0140-6736(10)62175-7