Siltuximab and hematologic malignancies. A focus in non Hodgkin lymphoma

  title={Siltuximab and hematologic malignancies. A focus in non Hodgkin lymphoma},
  author={Andrea Ferrario and Michele Merli and Claudia Basilico and Margherita Maffioli and Francesco Passamonti},
  journal={Expert Opinion on Investigational Drugs},
  pages={367 - 373}
ABSTRACT Introduction: The role of interleukin-6 (IL-6) in tumorigenesis and in particular in haematological malignancies is crucial. On the basis of the favourable results obtained in the subset of multicentric Castleman disease (MCD), Siltuximab, a chimeric, human-murine, immunoglobulin (Ig) Gk monoclonal antibody directed against human IL-6 has been evaluated in haematological malignancies such as multiple myeloma, myelodisplastic syndromes and non Hodgkin lymphomas. Areas covered: This… 
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Clinical Development of Siltuximab
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FDA Approval: Siltuximab for the Treatment of Patients with Multicentric Castleman Disease
The FDA granted full approval to siltuximab for the treatment of patients with multicentric Castleman disease who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative based on the results of a randomized, double-blind trial.
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Cytokine deregulation in hematological malignancies: clinical and biological implications.
  • R. Kurzrock
  • Biology, Medicine
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 1997
It is demonstrated that IL-6 levels are elevated in both relapsed and newly diagnosed Hodgkin's and non-Hodgkin's lymphoma and that these levels correlate with established prognostic features, and in diffuse large cell lymphoma, IL- 6 is an independent prognostic variable for both complete remission and failure-free survival.
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