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MCL overview

MCL overview

MCL typically manifests in the lymph nodes, intestinal tract, blood, and bone marrow.1

MCL accounts for approximately 6% of newly diagnosed cases of non-Hodgkin’s lymphoma (NHL).1 It is an aggressive form of NHL with a median overall survival (OS) of 47%.2 There are also subtypes of MCL, including indolent ones. The blastoid variant subtype is associated with a poor prognosis.3,4

MCL Incidence Rate by Disease Stage5

Most patients present with advanced MCL (stage II [bulky], stage III, and stage IV), for which there is no standard treatment regimen1,3,5

Evolution of treatment

Many challenges confront the treatment of patients with MCL. The majority of patients with MCL present with advanced stage disease that requires highly individualized courses of care, often involving systemic therapy. Additionally, a standard treatment regimen has not been established. Instead, there are guidelines to determine the best options for individual patients.1-3

The Mantle Cell International Prognostic Index (MIPI) is the standard resource for treatment planning. MIPI utilizes four independent prognostic factors to assign patients to low-risk, intermediate-risk, or high-risk categories to predict OS2,6:

  • Age
  • Performance status
  • Lactate dehydrogenase (LDH) levels
  • Leukocyte count

Based on a patient’s MIPI score, age and fitness, the European Society for Molecular Oncology (ESMO) recommends several different chemotherapy- or immunochemotherapy-based combination regimens as initial induction therapy.2

Next steps depend on a patient’s response to initial combination therapy, and may include second-line combination therapy, targeted therapy, monoclonal antibody therapy, or stem cell transplantation.2

 

MCL treatment approaches include1,2

Combination chemotherapy

Chemotherapy agents administered in specific sequences.

Targeted therapy

These small-molecule agents target key mechanisms involved in the molecular pathogenesis of MCL. Targeted therapies act through inhibition of intracellular signaling pathways, disruption of the tumor microenvironment or modulation of immune responses.

Monoclonal antibody therapy (mAb)

These agents target proteins on the surface of cells. mAbs are sometimes combined with combination chemotherapy or given as maintenance therapy following remission.

Stem cell transplantation

The European Society for Molecular Oncology (ESMO) recommends autologous stem cell transplantation as part of first-line therapy in young patients (patients under 60–65 years of age).

The ESMO does not recommend allogeneic stem cell transplantation as an upfront treatment option in MCL, but states that it may be considered for fit patients with MCL experiencing either relapse or refractory disease after appropriate line(s) of treatment.

Targeted therapy

The emergence of novel, targeted therapy options is evolving the treatment landscape of B-cell malignancies. These small-molecule agents target key mechanisms involved in the molecular pathogenesis of MCL.

  

Targeted therapies act through inhibition of intracellular signaling pathways, disruption of the tumor microenvironment or modulation of immune responses.2,7,8

B-cell malignancies

B-cell malignancies include most non-Hodgkin lymphomas (NHL), some leukaemias, and myelomas.9

B-cell signalling

Insights into key pathways have helped identify new targets for treating B-cell malignancies.7,10-12

Resources

Click here to access our resources section, which contains a range of useful documents and links with more information about B-cell malignancies.

B-cell signalling

Click below to download the B-cell malignancies brochure.

/sites/default/files/DA Brochure.pdf

References


  1. National Comprehensive Cancer Network. Non-Hodgkin’s Lymphomas, version 1. 2014.

  2. Dreyling M et al. ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma. Ann Oncol. 2013;24(4):857-877.

  3. Alinari L, Christian B, Baiocchi RA. Novel targeted therapies for mantle cell lymphoma. Oncotarget. 2012;3:203-211.

  4. Harris NL et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting—Airlie House, Virginia, November 1997. J Clin Oncol. 1999;17:3835-3849.

  5. Zhou Y et al. Incidence trends of mantle cell lymphoma in the United States between 1992-2004. Cancer. 2008;113:791-798.

  6. Hoster E et al. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood. 2008;111:558-565.

  7. Buggy JJ, Elias L. Bruton tyrosine kinase (BTK) and its role in B-cell malignancy. Int Rev Immunol. 2012;31:119-132.

  8. Jares P et al. Molecular pathogenesis of mantle cell lymphoma. J Clin Invest. 2012;122(10):3416-3423.

  9. Mitchell M et al. A multisource approach to improving epidemiology estimates: application to global B-cell malignancies. ISRN Oncol. 2012;2012:129713.

  10. Kil LP et al. Burton’s tyrosine kinase mediated signaling enhances leukemogenesis in a mouse model for chronic lymphocytic leukemia. Am J Blood Res. 2013;3:71-83.

  11. Burger JA et al. The microenvironment in mature B-cell malignancies: a target for new treatment strategies. Blood. 2009;114:3367-3375.

  12. ten Hacken E, Burger J. Molecular Pathways: Targeting the microenvironment in chronic lymphocytic leukemia focus on the B cell receptor. Clin Cancer Res. 2014;20:548-556.

  13. Eichhorst B et al. Chronic lymphocytic leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2011;22(Supplement 6):vi50-vi54.