Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Feb;16(1):8-18.
doi: 10.1007/s11899-021-00605-9. Epub 2021 Jan 28.

High-Risk Mantle Cell Lymphoma in the Era of Novel Agents

Edward Nabrinsky  1 , Alexey V Danilov  2 , Paul B Koller  3
Affiliations
Review

High-Risk Mantle Cell Lymphoma in the Era of Novel Agents

Edward Nabrinsky et al. Curr Hematol Malig Rep. 2021 Feb.

Abstract

Purpose of review: Mantle cell lymphoma (MCL) is a heterogenous disease with a variety of morphologic and genetic features, some of which are associated with high risk disease. Here we critically analyze the current state of the understanding of MCL's biology and its implications in therapy, with a focus on chemotherapy-free and targeted therapy regimens.

Recent findings: Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin's lymphoma, defined by a hallmark chromosomal translocation t(11;14) which leads to constitutive expression of cyclin D1. Recent discoveries in the biology of MCL have identified a number of factors, including TP53 mutations and complex karyotype, that lead to unresponsiveness to traditional chemoimmunotherapy and poor outcomes. Bruton tyrosine kinase inhibitors, BH3-mimetics and other novel agents thwart survival of the neoplastic B-cells in a manner independent of high-risk mutations and have shown promising activity in relapsed/refractory MCL. These therapies are being investigated in the frontline setting, while optimal responses to chemotherapy-free regimens, particularly in high-risk disease, might require combination approaches. High-risk MCL does not respond well to chemoimmunotherapy. Targeted agents are highly active in the relapsed refractory setting and show promise in high-risk disease. Novel approaches may soon replace the current standard of care in both relapsed and frontline settings.

Keywords: Drug resistance; High-risk MCL; MCL; Mantle cell lymphoma; Novel therapy; TP53; Targeted therapy.

PubMed Disclaimer

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
    1. Rosenwald A, Wright G, Wiestner A, Chan WC, Connors JM, Campo E, et al. The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell. 2003;3(2):185–97. https://doi.org/10.1016/s1535-6108(03)00028-x . - DOI - PubMed
    1. Stefancikova L, Moulis M, Fabian P, Ravcukova B, Vasova I, Muzik J, et al. Loss of the p53 tumor suppressor activity is associated with negative prognosis of mantle cell lymphoma. Int J Oncol. 2010;36(3):699–706. https://doi.org/10.3892/ijo_00000545 . - DOI - PubMed
    1. Bea S, Valdes-Mas R, Navarro A, Salaverria I, Martin-Garcia D, Jares P, et al. Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. Proc Natl Acad Sci U S A. 2013;110(45):18250–5. https://doi.org/10.1073/pnas.1314608110 . - DOI - PubMed - PMC
    1. Salaverria I, Royo C, Carvajal-Cuenca A, Clot G, Navarro A, Valera A, et al. CCND2 rearrangements are the most frequent genetic events in cyclin D1(−) mantle cell lymphoma. Blood. 2013;121(8):1394–402. https://doi.org/10.1182/blood-2012-08-452284 . - DOI - PubMed - PMC
    1. Jain P, Wang M. Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management. Am J Hematol. 2019;94(6):710–25. https://doi.org/10.1002/ajh.25487 . - DOI - PubMed

Substances

LinkOut - more resources