Mantle Cell Lymphoma: Evolving Frontline Treatment Strategies

Authors

  • Inna Y. Gong, MD Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  • John Kuruvilla, MD Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  • Michael Crump, MD Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada Department of Medicine, University of Toronto, Toronto, Ontario, Canada

DOI:

https://doi.org/10.58931/cht.2024.3251

Abstract

Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma (NHL) that accounts for 3-10% of new NHL cases in Canada. The clinical course of MCL is heterogeneous, ranging from indolent behavior that does not require therapy for years, to highly aggressive disease with limited prognosis. As such, the 2022 International Consensus Classification (ICC) and World Health Organization (WHO) classifications subdivide MCL into two categories: 1) indolent MCL, which is characterized by blood involvement, splenomegaly without nodal involvement, or low-burden nodal involvement (mutated immunoglobulin heavy chain [IGHV], SOX11 negative, low Ki67 proliferative index); and 2) aggressive MCL, which is characterized by pleomorphic and blastoid morphologic appearance, TP53 aberrancy, high Ki67, and unmutated IGHV.

While traditionally, patients with MCL had a median overall survival (OS) of only 3 to 5 years, there has been significant improvement over the last two decades, owing to chemoimmunotherapy with rituximab, cytarabine-based induction regimens, addition of consolidative autologous stem cell transplant (ASCT), rituximab maintenance, and the advent of novel targeted therapies (including Bruton kinase inhibitors [BTKi], venetoclax, and lenalidomide) in the relapsed setting. Despite these advances, MCL remains incurable even with aggressive therapy, and most patients will invariably relapse. As such, prospective studies integrating novel therapies with either a chemotherapy backbone or evaluating chemotherapy-free regimens are ongoing, aiming to improve outcomes and reduce toxicities. This review summarizes the current understanding of disease prognostication, treatment options, and novel therapeutic strategies that will reshape the treatment paradigm of MCL in the near future.

Author Biographies

Inna Y. Gong, MD, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada Department of Medicine, University of Toronto, Toronto, Ontario, Canada

Dr. Inna Gong is a Lymphoma fellow completing a combined clinical and post-doctoral fellowship focused on advanced therapies for lymphoid malignancies at Princess Margaret Hospital. She is enrolled in the Eliot Philipson Clinician Scientist Training Program and Clinical Investigator Program at University of Toronto. She has earned a PhD in Clinical Pharmacology from Western University and an MD from the University of Toronto, followed by recent completion of her Royal College certification in Internal Medicine and Hematology. Her research focuses on delineating immuno-metabolomic variation among patients with lymphoid malignancies, as well as identifying new immune-based biomarkers for predicting therapeutic outcomes.

John Kuruvilla, MD, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada Department of Medicine, University of Toronto, Toronto, Ontario, Canada

Dr. John Kuruvilla is an Associate Professor of Medicine at the University of Toronto and a hematologist in the Division of Medical Oncology and Hematology at the Princess Margaret Cancer Centre in Toronto. He is a member of the Lymphoma, Autologous Transplant and Immune Effector Cell Therapy programs. Dr. Kuruvilla’s research interest is the development of novel therapeutics in lymphoid malignancies and incorporating translational research into clinical trials. He is the Lymphoma Co-chair for the Canadian Cancer Trials Group (CCTG) as well as the Chair of the Scientific Advisory Board of Lymphoma Canada.

Michael Crump, MD, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada Department of Medicine, University of Toronto, Toronto, Ontario, Canada

Dr. Michael Crump is a Hematologist in the Division of Medical Oncology and Hematology at Princess Margaret Cancer Centre, and Professor of Medicine at the University of Toronto. He was the Co-chair of the Hematology Site Group of the CCTG for many years and the Co-chair of the Lymphoma working group. His research interests include the development of new therapies for lymphomas including bispecific antibodies and chimeric antigen receptor CAR T-cells and the application of autologous stem cell transplantation.

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Gong IY, Kuruvilla J, Crump M. Mantle Cell Lymphoma: Evolving Frontline Treatment Strategies. Can Hematol Today [Internet]. 2024 Jun. 27 [cited 2024 Oct. 22];3(2):5–21. Available from: https://canadianhematologytoday.com/article/view/3-2-gong_et_al

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