Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma.

Abstract

PURPOSE:

We conducted an international, randomized, phase III trial to evaluate the efficacy and safety of consolidation with yttrium-90 ((90)Y)-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 (90)Y-ibritumomab tiuxetan (rituximab 250 mg/m(2) on day -7 and day 0 followed on day 0 by (90)Y-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. (90)Y-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 (90)Y-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 (90)Y-ibritumomab tiuxetan was hematologic, and grade 3 or 4 infections occurred in 8% of patients.

CONCLUSION:

Consolidation of first remission with (90)Y-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.

• Authors: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 26 Issue 32 Pg. 5156-64 (Nov 10 2008) ISSN: 1527-7755 [Electronic] United States
• PMID: 18854568 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Antigens, CD20
• Rituximab
• ibritumomab tiuxetan

Topics

• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage, adverse effects, therapeutic use)
• Antibodies, Monoclonal, Murine-Derived
• Antigens, CD20 (analysis)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Canada
• Chemotherapy, Adjuvant
• Disease-Free Survival
• Europe
• Female
• Humans
• Lymphoma, Follicular (drug therapy, immunology, pathology, radiotherapy)
• Male
• Middle Aged
• Neoplasm Staging
• Radioimmunotherapy
• Radiotherapy, Adjuvant
• Rituximab
• Time Factors
• Treatment Outcome