Current Treatment Options in Oncology

, Volume 13, Issue 1, pp 82–101

Emerging Therapeutic Targets in Diffuse Large B-Cell Lymphoma

  • Murali Janakiram
  • Venu K. Thirukonda
  • Matthew Sullivan
  • Adam M. Petrich
Lymphomas (L Gordon, Section Editor)

DOI: 10.1007/s11864-011-0178-9

Cite this article as:
Janakiram, M., Thirukonda, V.K., Sullivan, M. et al. Curr. Treat. Options in Oncol. (2012) 13: 82. doi:10.1007/s11864-011-0178-9

Opinion statement

The standard front-line treatment of Diffuse Large B-Cell Lymphoma (DLBCL) remains Rituximab combined with multi-agent cytotoxic chemotherapy. In spite of high response rates to this therapy, relapsed/refractory disease is observed in up to 40% of patients. It is our opinion that additional chemoimmunotherapy, followed by high-dose therapy with autologous stem cell transplant (HDT-ASCT) for responsive disease, is the optimal therapy for these patients. However, many patients cannot tolerate HDT-ASCT, or have relapsed/refractory disease in spite of it. These patients have a poor overall prognosis, and there is no clear consensus as to how these patients should be treated. Over the past decade, significant advances have been made in the understanding of the molecular genesis and subtyping of DLBCL, leading to the identification of multiple pathways and molecules that can be targeted for clinical benefit. Examples include Bcl-2, Bcl-6, cell surface markers, and myriad molecules in both the B-Cell receptor and PI3K/Akt/mTOR pathways. As agents targeting these molecules and pathways progress from preclinical models to early clinical trials, more is learned about what might predict for response to these agents, such as cell of origin classification, and/or expression of relevant molecular markers, as measured by immunohistochemistry or gene expression profiling. Both the successes and failures of these novel targeted agents promise to dramatically refine, improve, and individualize the classification and treatment of DLBCL. Therefore, it is our opinion that patients with relapsed/refractory DLBCL are an ideal population for clinical trials due to both the lack of standardized treatment, and the recent advancements in pathobiology and early-phase treatment options.

Keywords

Diffuse Large B-Cell Lymphoma (DLBCL) Rituximab Multi-agent cytotoxic chemotherapy Chemoimmunotherapy By high-dose therapy with autologous stem cell transplant (HDT-ASCT) Therapeutic targets Non-Hodgkin Lymphoma (NHL) 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Murali Janakiram
    • 1
    • 2
    • 3
  • Venu K. Thirukonda
    • 1
    • 2
    • 3
  • Matthew Sullivan
    • 4
  • Adam M. Petrich
    • 5
  1. 1.Department of OncologyMontefiore Medical CenterBronxUSA
  2. 2.Division of Hematology, Department of MedicineMontefiore Medical CenterBronxUSA
  3. 3.Albert Einstein Cancer CenterAlbert Einstein College of MedicineBronxUSA
  4. 4.Department of MedicineMontefiore Medical CenterBronxUSA
  5. 5.Division of Hematology/Oncology, Feinberg School of MedicineNorthwestern UniversityChicagoUSA

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