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The Oncologist, Vol. 14, No. suppl_2, 1-3, October 2009; doi:10.1634/theoncologist.2009-S2-1
© 2009 AlphaMed Press

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Introduction

Angelika Bischof Delaloyea, Peter S. Contib, Christian Gisselbrechtc, Stephanie A. Gregoryd

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. Non-Hodgkin's lymphoma • Radioimmunotherapy • Anti-CD20 antibody • PET/CT imaging • Complete response

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.

An expert panel of 44 physicians (including hemato-oncologists, radiologists, and nuclear medicine physicians) recently met at the 6th International Workshop on Nuclear Oncology, which was held April 17–19, 2008. The scientific committee who chaired this workshop, alongside the distinguished faculty who presented data at this meeting, have prepared this supplement to summarize and explore the emerging data and changing protocols for the diagnosis and treatment of non-Hodgkin's lymphoma (NHL) and discuss the evolving role of radioimmunotherapy (RIT) in the treatment of such malignancies.

NHL encompasses a number of different B-cell lymphomas that can be separated into two groups: aggressive, such as diffuse large B-cell lymphoma and mantle cell lymphoma; and indolent, such as follicular lymphoma (FL) [1, 2]. There are a number of treatment options for NHL depending on the nature of the disease and the health of the patient; therefore, it is important to individualize the therapy for the patient (Fig. 1). The first article of this supplement, entitled "Harnessing the energy: Development of radioimmunotherapy for patients with non-Hodgkin's lymphoma," focuses on this issue [3]. Because of the intensive nature of some of the regimens for NHL, such as high-dose chemotherapy, it is important to balance the benefit of providing therapy with patient quality of life.


Figure 1
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  		Figure 1. Non-Hodgkin's lymphoma patient selection and treatment algorithm.

Abbreviations: CECT, contrast-enhanced computed tomography; CR, complete response; FDG-PET, 18F-fluoro-2-deoxyglucose positron emission tomography; PET/CT, 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography; PR, partial response; SCT, stem cell transplantation.

 
Although there is no consensus on first-line treatment for FL, there have been a number of advances in the past decade that have improved treatment outcomes. Studies have shown that attaining a complete response (CR) in FL is a prognostic factor for survival. A large retrospective analysis of factors that affect survival in FL patients concluded that attaining a CR with initial therapy was the factor that was most predictive of a longer overall survival duration [4, 5]. Therefore, treatment strategies that maximize CR rates and eliminate residual disease are needed to improve survival outcomes in patients with FL. The second article in this supplement, "Rationale for consolidation to improve progression-free survival in patients with non-Hodgkin's lymphoma: A review of the evidence," outlines the approaches to attain a CR in FL, focusing on consolidation treatment following first-line induction treatment [6]. The role of yttrium-90 (90Y)-ibritumomab tiuxetan (Zevalin®; Spectrum Pharmaceuticals, Inc., Irvine, CA; Bayer Schering Pharma AG, Berlin, Germany), a radioactively labeled antiCD20 monoclonal antibody, is described in this article, which also includes results from the recent international, multicenter, phase III First-line Indolent Trial. That trial demonstrated impressive survival benefits for patients with FL who were treated with 90Y-ibritumomab tiuxetan as consolidation therapy in the first-line setting [7]. These data led to the European Medicines Agency approval of 90Y-ibritumomab tiuxetan for consolidation therapy following remission induction in previously untreated patients with FL.

Patient selection for therapy is facilitated by imaging technology, specifically 18F-fluoro-2-deoxyglucose positron emission tomography (PET) and computed tomography (CT). There is an expanding role for PET/CT in the diagnosis, staging, and evaluation of response to therapy [8–11]. In the third article, entitled "Expert opinions on positron emission tomography and computed tomography imaging in lymphoma," Dominique Delbeke et al. [12] discuss the new guidelines for staging and response criteria of NHL and provide expert opinion on how best to standardize the use of PET/CT for making therapy decisions.

Historically, the only curative option for eligible patients with NHL has been stem cell transplantation (SCT); however, this treatment option is usually combined with a highly toxic, myeloablative regimen of high-dose chemotherapy and/or total-body irradiation [13]. Because older patients make up the majority of the NHL population and may not be able to withstand these toxicities, and because some patients may still relapse as a result of incomplete eradication of residual disease [14], there is a need for a new approach to myeloablative therapy that is both effective and well tolerated. The final article, "Radioimmunotherapy for stem cell transplantation in non-Hodgkin's lymphoma: In pursuit of a complete response," outlines the RIT studies that have investigated its use in this setting so far [15]. These data suggest that the use of RIT alone or in combination with chemotherapy in this setting can improve clinical outcome, with no added toxicity for patients undergoing SCT therapy.

In this rapidly evolving field, we hope that you find the expert opinion presented in this supplement informative and useful in your clinical practice.


   AUTHOR CONTRIBUTIONS
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 Author Contributions
References
 
Conception/design: Angelika Bischof Delaloye, Peter S. Conti, Stephanie A. Gregory

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.


   REFERENCES
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 Author Contributions
 References
 

  1. Armitage JO. Treatment of non-Hodgkin's lymphoma. N Engl J Med 1993;328:1023–1030.[Free Full Text]
  2. Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin's lymphomas: Clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project. J Clin Oncol 1998;16:2780–2795.[Abstract]
  3. Gregory SA, Hohloch K, Gisselbrecht C et al. Harnessing the energy: Development of radioimmunotherapy for patients with non-Hodgkin's lymphoma. The Oncologist 2009;14(suppl 2):4–16.[Abstract/Free Full Text]
  4. Bachy E, Brice P, Fournier M et al. Long term follow-up of the GELF86 French and Belgian trials: Complete remission after first line treatment with conventional chemotherapy in newly diagnosed follicular lymphoma patients correlates with prolonged overall survival compared with partial remission [abstract 2590]. Blood 2008;112:898.
  5. Davidge-Pitts M, Dansey R, Bezwoda WR. Prolonged survival in follicular non Hodgkins lymphoma is predicted by achievement of complete remission with initial treatment: Results of a long term study with multivariate analysis of prognostic factors. Leuk Lymphoma 1996;24:131–140.[Medline]
  6. Morschhauser F, Dreyling M, Rohatiner A et al. Rationale for consolidation to improve progression-free survival in patients with non-Hodgkin's lymphoma: A review of the evidence. The Oncologist 2009;14(suppl 2):17–29.[Abstract/Free Full Text]
  7. Morschhauser F, Radford J, Van Hoof A et al. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol 2008;26:5156–5164.[Abstract/Free Full Text]
  8. Blodgett TM, Meltzer CC, Townsend DW. PET/CT: Form and function. Radiology 2007;242:360–385.[Abstract/Free Full Text]
  9. Jhanwar YS, Straus DJ. The role of PET in lymphoma. J Nucl Med 2006;47:1326–1334.[Abstract/Free Full Text]
  10. Rohren EM, Turkington TG, Coleman RE. Clinical applications of PET in oncology. Radiology 2004;231:305–332.[Abstract/Free Full Text]
  11. von Schulthess GK, Steinert HC, Hany TF. Integrated PET/CT: Current applications and future directions. Radiology 2006;238:405–422.[Abstract/Free Full Text]
  12. Delbeke D, Stroobants S, de Kerviler E et al. Expert opinions on positron emission tomography and computed tomography imaging in lymphoma. The Oncologist 2009;14(suppl 2):30–40.[Abstract/Free Full Text]
  13. Jantunen E, Mahlamäki E, Nousiainen T. Feasibility and toxicity of high-dose chemotherapy supported by peripheral blood stem cell transplantation in elderly patients (≥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]
  14. Gianni AM, Berinstein NL, Evans PA et al. Stem-cell transplantation in non-Hodgkin's lymphoma: Improving outcome. Anticancer Drugs 2002;13(suppl 2):S35–S42.[Medline]
  15. Gisselbrecht C, Vose J, Nademanee A et al. Radioimmunotherapy for stem cell transplantation in non-Hodgkin's lymphoma: In pursuit of a complete response. The Oncologist 2009;14(suppl 2):41–51.[Abstract/Free Full Text]




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