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aCentre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; bUniversity of Southern California, Los Angeles, CA, USA; cHôpital Saint-Louis, Paris, France; dRush University Medical Center, Chicago, IL, USA
Key Words. Follicular lymphoma • Yttrium-90-ibritumomab tiuxetan • Iodine-131-tositumomab • Stem cell therapy • First-line consolidation therapy • PET/CT guidelines
Correspondence: Angelika Bischof Delaloye, M.D., Department of Nuclear Medicine, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland. Telephone: 41-21-314-43-46/47; Fax: 41-21-314-43-49; e-mail: Angelika.BischofDelaloye{at}chuv.ch
Received March 27, 2009; accepted for publication June 1, 2009.
Disclosures: Angelika Bischof Delaloye: Consultant/advisory role: Bayer Schering Pharma AG; Peter S. Conti: Honoraria: Bayer; Christian Gisselbrecht: Research funding/contracted research: Bayer Schering Pharma; Stephanie A. Gregory: Honoraria: GlaxoSmithKline, Genentech.
The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.
The International Workshop on Nuclear Oncology scientific committee's aim for this supplement was to offer an overview of the new standards of care for non-Hodgkin's lymphoma (NHL) and provide an update of the most recent data and emerging concepts that continue to change the way this disease is treated. Radioimmunotherapy (RIT) has revolutionized the treatment of NHL and has shown its potential for extending the lives of patients with rituximab-relapsed or rituximab-refractory follicular lymphoma (FL). The long-term remission and high response rates achieved with RIT were discussed in a recent commentary, highlighting progression-free survival curve plateaus of >40% in some RIT studies [1]. The recent pivotal First-line Indolent Trial (FIT) is exemplary of the role that RIT can play in the treatment of patients with FL.
FIT reported a remarkable survival benefit for the use of yttrium-90 (90Y)-ibritumomab tiuxetan as consolidation therapy for patients with FL and represents a new and important treatment approach for these patients [2]. The superior progression-free survival can be attributed to the high conversion rate of partial responses to complete responses (CRs), because attainment of a CR is associated with longer survival [3, 4]. Furthermore, 90Y-ibritumomab tiuxetan consolidation therapy showed a favorable tolerability profile with no unexpected toxicities; as a result, RIT in combination with a variety of treatment regimens may provide benefit to a wider range of patients and could prove to be a valid alternative to stem cell therapy as a potential curative treatment.
Based on these data, the European Medicines Agency has approved the use of 90Y-ibritumomab tiuxetan as consolidation therapy following remission induction in previously untreated patients with FL. Guidelines have been published that recommend the use of RIT (and in particular 90Y-ibritumomab tiuxetan) in first-line consolidation therapy [5–7], especially for patients in whom a significant survival benefit and possible cure are feasible [8]. It remains to be seen whether 90Y-ibritumomab tiuxetan has the potential to treat aggressive lymphomas; however, the data appear promising.
Although RIT consolidation therapy is effective, the role of stem cell therapy will continue to play an important part in the treatment of NHL because it is still the only known and validated curative option, with high CR rates [9–11]. Currently, the autologous stem cell transplantation (ASCT) regimen includes a highly toxic myeloablative regimen (such as high-dose chemotherapy and/or total-body irradiation), which many patients cannot tolerate [12]. RIT-containing pretransplant therapies are a highly effective treatment strategy, providing better clinical outcomes for patients with indolent lymphomas when compared with historical data of high-dose chemotherapy pretransplant regimens [13]. Preliminary data in patients with aggressive lymphomas treated with RIT-containing pretransplant regimens and ASCT are also promising [14, 15]. RIT once again has been demonstrated to have the potential to broaden the treatment choice for patients who traditionally would be ineligible for stem cell therapy.
Because attaining a CR is important for longer survival, identifying patients who achieve this becomes more important. Recently, changes were introduced to the guidelines for defining treatment response in lymphoma that reflected the increasing use of positron emission tomography in treatment centers [16, 17]. Integration of positron emission tomography into these guidelines has removed the need for the unconfirmed response status and simplified the management of NHL patients [16, 17]. These guidelines are currently based on the authors' and scientific committee's expertise, and further studies are required to validate them. As these studies continue, the guidelines will continue to evolve and will hopefully improve the diagnosis and management of all lymphoma patients.
In conclusion, this supplement provides clinicians with an overview of the current diagnosis and treatment options for patients with FL. The approval of 90Y-ibritumomab tiuxetan for first-line consolidation therapy after remission therapy in FL patients represents a step forward for the treatment of NHL. A greater number of patients will be able to receive RIT consolidation as their first treatment choice, paving the way for a new standard of care.
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Provision of study materials or patients: Christian Gisselbrecht, Stephanie A. Gregory
Collection/assembly of data: Peter S. Conti, Christian Gisselbrecht
Data analysis and interpretation: Peter S. Conti, Christian Gisselbrecht
Manuscript writing: Angelika Bischof Delaloye, Peter S. Conti, Christian Gisselbrecht, Stephanie A. Gregory
Final approval of manuscript: Angelika Bischof Delaloye, Peter S. Conti, Christian Gisselbrecht, Stephanie A. Gregory
The authors take full responsibility for the scope, direction, and content of the manuscript and have approved the submitted manuscript. They would like to thank Lynda Chang, Ph.D., at Complete Health Vizion for her assistance in the preparation and revision of the draft manuscript, based on detailed discussion and feedback from all the authors. Editorial assistance was supported by a grant from Bayer HealthCare Pharmaceuticals.
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60 years) with non-Hodgkin's lymphoma: Comparison with patients <60 years treated within the same protocol. Bone Marrow Transplant 2000;26:737–741.[CrossRef][Medline]
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