Biological Therapy Doublets: Pairing Rituximab with Interferon, Lenalidomide, and Other Biological Agents in Patients wi
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LYMPHOMAS (J ARMITAGE AND P MCLAUGHLIN, SECTION EDITORS)
Biological Therapy Doublets: Pairing Rituximab with Interferon, Lenalidomide, and Other Biological Agents in Patients with Follicular Lymphoma Eva Kimby
# Springer Science+Business Media, LLC 2012
Abstract Rituximab (R) is a monoclonal antibody with high therapeutic efficacy in low-grade CD20+ lymphoma. The combination of R with chemotherapy is the most common treatment option for patients with follicular lymphoma (FL). The efficacy of R has also been shown to be augmented, when used in combinations with biologicals such as interferonalpha-2a (IFN), bortezomib, or lenalidomide. The best combination of these drugs are not well defined and a better understanding of pharmacokinetics and timing of drugs relative to the rituximab infusion is crucial. Other new targeted agents, such as inhibitors of BTK and PI3Kdelta, have also been promising in FL. Translational research questions should be added to clinical trial protocols to increase the knowledge on how the tumor microenvironment and the host immune system affect the response to the different drugs and combinations with the aim of a more individualized therapy. Keywords Follicular lymphoma . Biological therapy . Rituximab . Interferon . Lenalidomide . Bortezomib . Tumor immunoenvironment
Introduction Follicular lymphoma (FL) is, besides CLL, the most common of the indolent non-Hodgkin lymphomas (NHL). Most FL patients present with advanced stage disease, but the clinical course is highly variable with some patients remaining E. Kimby (*) Division of Hematology, M54, Karolinska University Hospital, 141 96 Stockholm, Sweden e-mail: [email protected] E. Kimby Division of Hematology, Department of Medicine at Huddinge, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
symptom-free for many years, while others have rapidly progressive disease. The biological background for this heterogeneity remains largely unknown. Asymptomatic patients are often managed with a “watch and wait” strategy until progression [1, 2], but there is no consensus regarding the optimal timing or best type of initial therapy. Treatment is mostly initiated if disease-related symptoms occur, such as bulky or progressive lymphadenopathy/hepato/splenomegaly, compromised bone marrow or risk for organ compromise from nodal compression. Since the introduction of the anti-CD20 monoclonal antibody rituximab (R), the survival for FL patients has improved. Single-agent rituximab was initially approved for relapsed or refractory follicular lymphomas. Today most patients receive rituximab in combination with chemotherapy as initial treatment. The disease is however still characterized by repeated relapses and retreatments and many patients will die from their disease. Several large randomized trials have compared cytostatic regimens with the same in combination with R, all showing benefit of the R-combination [3, 4]. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been claimed to be the most effective regime
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