Originally published as JCO Early Release 10.1200/JCO.2008.17.2015 on October 14 2008

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Phase III Trial of Consolidation Therapy With Yttrium-90–Ibritumomab Tiuxetan Compared With No Additional Therapy After First Remission in Advanced Follicular Lymphoma

Franck Morschhauser, John Radford, Achiel Van Hoof, Umberto Vitolo, Pierre Soubeyran, Herve Tilly, Peter C. Huijgens, Arne Kolstad, Francesco d’Amore, Marcos Gonzalez Diaz, Mario Petrini, Catherine Sebban, Pier Luigi Zinzani, Marinus H.J. van Oers, Wim van Putten, Angelika Bischof-Delaloye, Ama Rohatiner, Gilles Salles, Jens Kuhlmann, Anton Hagenbeek

From the Centre Hospitalier Universitaire, Lille; Institut Bergonié, Bordeaux; Centre Henri Becquerel, Rouen; Centre Léon Bérard, Lyon; Centre Hospitalier Lyon Sud, Pierre Bénite, France; Christie Hospital and University of Manchester, Manchester; St Bartholomew's Hospital, London, United Kingdom; General Hospital St-Jan, Brugge, Belgium; Azienda Universitaria Ospedaliera S. Giovanni Battista, Torino; Azienda Ospedaliera Pisana, Pisa; Institute of Hematology "Seràgnoli," University of Bologna, Bologna, Italy; VU University Medical Center; Academic Medical Center, Amsterdam; Erasmus University Medical Center/Dutch Hemato-Oncology Group (HOVON), Rotterdam; University Medical Center/HOVON, Utrecht, the Netherlands; The Norwegian Radium Hospital, Oslo, Norway; Århus University Hospital, Århus, Denmark; Hospital Clínico Universitario de Salamanca, Salamanca, Spain; Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; and Bayer Schering Pharma AG, Berlin, Germany

Corresponding author: Anton Hagenbeek, MD, PhD, Department of Hematology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands; e-mail: a.hagenbeek{at}umcutrecht.nl

Purpose We conducted an international, randomized, phase III trial to evaluate the efficacy and safety of consolidation with yttrium-90 (⁹⁰Y)–ibritumomab tiuxetan in patients with advanced-stage follicular lymphoma in first remission.

Patients and Methods Patients with CD20⁺ stage III or IV follicular lymphoma, who achieved a complete response (CR)/unconfirmed CR (CRu) or partial response (PR) after first-line induction treatment, were randomly assigned to receive ⁹⁰Y-ibritumomab tiuxetan (rituximab 250 mg/m² on day –7 and day 0 followed on day 0 by ⁹⁰Y-ibritumomab tiuxetan 14.8 MBq/kg; maximum of 1,184 MBq) or no further treatment (control). The primary end point was progression-free survival (PFS), which was calculated from the time of random assignment.

Results A total of 414 patients (consolidation, n = 208; control, n = 206) were enrolled at 77 centers. ⁹⁰Y-ibritumomab tiuxetan consolidation significantly prolonged median PFS (after a median observation time of 3.5 years) in all patients (36.5 v 13.3 months in control arm; hazard ratio [HR] = 0.465; P < .0001) and regardless of whether patients achieved PR (29.3 v 6.2 months in control arm; HR = 0.304; P < .0001) or CR/CRu (53.9 v 29.5 months in control arm; HR = 0.613; P = .0154) after induction treatment. Median PFS with consolidation was prolonged in all Follicular Lymphoma International Prognostic Index risk subgroups. After ⁹⁰Y-ibritumomab tiuxetan consolidation, 77% of patients in PR after induction converted to CR/CRu, resulting in a final CR rate of 87%. The most common toxicity with ⁹⁰Y-ibritumomab tiuxetan was hematologic, and grade 3 or 4 infections occurred in 8% of patients.

Conclusion Consolidation of first remission with ⁹⁰Y-ibritumomab tiuxetan in advanced-stage follicular lymphoma is highly effective with no unexpected toxicities, prolonging PFS by 2 years and resulting in high PR-to-CR conversion rates regardless of type of first-line induction treatment.

published online ahead of print atwww.jco.org on October 13, 2008

Supported by Bayer Schering Pharma AG, Berlin, Germany.

Presented in part at the 49th Annual Meeting of the American Society of Hematology, December 8-11, 2007, Atlanta, GA.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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