Case Report
Lymphoma and Immunosuppression: A Report of a Case Associated With Efalizumab Therapy

https://doi.org/10.3816/CLML.2010.n.011Get rights and content

Abstract

Lymphomas have been associated with immunodeficiency disorders, including those acquired secondary to the use of immunosuppressants for autoimmune disorders and for the prevention of graft rejection. Biologic agents have also been associated with the development of lymphoproliferative disorders. We report the case of Epstein-Barr Virus–negative diffuse large B-cell lymphoma associated with efalizumab, a monoclonal antibody that inhibits T-cell activity. Discontinuation of efalizumab resulted in a partial remission of lymphoma, although administration of chemotherapy was ultimately required. The use of immunomodulators must be tempered with the knowledge of their effect on the immune system and their association with lymphoproliferative disorders.

Introduction

Well-established risk factors for lymphoma include uncommon immunodeficiency disorders such as hypogammaglobulinemia, HIV/AIDS, and organ transplantation. B-cell lymphomagenesis may be attributed to local T-cell–dependent antigen-driven proliferation of B cells that eventually become monoclonal and develop into lymphoma. Resistance to apoptosis may be acquired in autoimmune disorders and may be mediated by BCL2 expression, activation of nuclear factor–κB by inflammatory cytokines and growth factors as well as abnormalities in the expression of B-cell activating factor.1

Autoimmune disorders such as rheumatoid arthritis, systemic lupus, and Sjogren syndrome have been shown to have an increased risk of lymphoproliferative disorders.1, 2 An increased risk of cutaneous T-cell lymphomas and Hodgkin lymphoma has also been described with psoriasis.3 In addition to any increased risk of malignancy conferred by individual rheumatic diseases, there is also a potential risk related to the duration of exposure to immunosuppressive drugs such as azathioprine, methotrexate, cyclophosphamide, and chlorambucil.4, 5, 6, 7, 8, 9 Biologic response modifiers such as infliximab and adalimumab have also been associated with a possible risk of the development of lymphoproliferative disease.10 We describe a case of a patient with psoriasis who developed lymphoma while receiving the biologic drug efalizumab that spontaneously regressed on withdrawal of the immunosuppressive agent.

Section snippets

Case Report

A 55-year-old black male on weekly efalizumab therapy for 2 years to treat generalized psoriasis presented with a 4-week history of fatigue, back pain, and weight loss of 11 kg. There was no history of fever, night sweats, headache, or seizures. His past medical history was significant for diabetes mellitus, hypertension, autoimmune hypothyroidism, and psoriasis. Concomitant medications included metoprolol, hydrochlorothiazide, levothyroxine, metformin, and pioglitazone.

His physical examination

Discussion

Efalizumab is a humanized monoclonal antibody that binds to the CD11a subunit of lymphocyte function–associated antigen 1 (LFA-1) on memory T cells, preventing LFA-1 binding to its ligand intercellular adhesion molecule 1 (ICAM-1) on vascular endothelial cells and keratinocytes. It rapidly reduces available CD11a binding sites and expression of CD11a on the surface of T lymphocytes. Downregulation of cell surface molecules such as VLA-4, 7 integrin, and L selectin limits the ability of T cells

Conclusion

Biologic agents are an efficacious way to treat various chronic inflammatory states but are also associated with the development of lymphoproliferative disorders. They should be used with caution and prudence in an already immunosuppressed patient population. Vigilance and a high index of suspicion are warranted in the care and continued follow-up of patients on long-term treatment with these medications. Further studies looking into these agents' oncologic potential should be encouraged.

Disclosures

Alan Menter is on the advisory board and serves as a consultant, investigator and speaker for Abbott Laboratories, Amgen, Astellas Pharma Inc., Centocor, Inc., Genentech, Inc., Warner Chilcott, and Wyeth Pharmaceuticals. He is on the advisory board, serves as a consultant, and has been on a Speaker's Bureau for Galderma, is an investigator for Allergan, Asubio Pharmaceuticals, Inc., Celgene Corporation, DUSA Pharmaceuticals, Inc., Eli Lilly and Company, Novartis Pharmaceuticals Corporation,

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