Emerging therapies in mantle cell lymphoma

J Hematol Oncol. 2020 Jun 17;13(1):79. doi: 10.1186/s13045-020-00914-1.

Abstract

Mantle cell lymphoma (MCL) is a rare, B cell non-Hodgkin's lymphoma with highly heterogeneous clinical presentation and aggressiveness. First-line treatment consists of intensive chemotherapy with autologous stem cell transplant for the fit, transplant eligible patients, or less intensive chemotherapy for the less fit (and transplant-ineligible) patients. Patients eventually relapse with a progressive clinical course. Numerous therapeutic approaches have emerged over the last few years which have significantly changed the treatment landscape of MCL. These therapies consist of targeted approaches such as BTK and BCL2 inhibitors that provide durable therapeutic responses. However, the optimum combination and sequencing of these therapies is unclear and is currently investigated in several ongoing studies. Furthermore, cellular therapies such as chimeric antigen receptor (CAR) T cells and bispecific T cell engager (BiTe) antibodies have shown impressive results and will likely shape treatment approaches in relapsed MCL, especially after failure with BTK inhibitors. Herein, we provide a comprehensive review of past and ongoing studies that will likely significantly impact our approach to MCL treatment in both the frontline (for transplant eligible and ineligible patients) as well as in the relapsed setting. We present the most up to date results from these studies as well as perspectives on future studies in MCL.

Keywords: BCL2; BTK; BiTe; CART; Mantle cell lymphoma.

Publication types

  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors
  • Antibodies, Bispecific / therapeutic use
  • Antineoplastic Agents, Immunological / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors
  • Drugs, Investigational / therapeutic use
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunoconjugates / therapeutic use
  • Immunotherapy, Adoptive
  • Lenalidomide / therapeutic use
  • Lymphoma, Mantle-Cell / drug therapy
  • Lymphoma, Mantle-Cell / therapy*
  • Neoplasm Proteins / antagonists & inhibitors
  • Proteasome Inhibitors / therapeutic use
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Recurrence
  • Salvage Therapy
  • Therapies, Investigational*

Substances

  • Antibodies, Bispecific
  • Antineoplastic Agents, Immunological
  • Drugs, Investigational
  • Immunoconjugates
  • Neoplasm Proteins
  • Proteasome Inhibitors
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • Lenalidomide