From bench to bedside: the past, present and future of therapy for systemic paediatric ALCL, ALK

Br J Haematol. 2019 Jun;185(6):1043-1054. doi: 10.1111/bjh.15763. Epub 2019 Jan 25.

Abstract

Anaplastic large cell lymphoma (ALCL) is a T cell Non-Hodgkin Lymphoma that mainly presents in paediatric and young adult patients. The majority of cases express a chimeric fusion protein resulting in hyperactivation of anaplastic lymphoma kinase (ALK) as the consequence of a chromosomal translocation. Rarer cases lack expression of ALK fusion proteins and are categorised as ALCL, ALK-. An adapted regimen of an historic chemotherapy backbone is still used to this day, yielding overall survival (OS) of over 90% but with event-free survival (EFS) at an unacceptable 70%, improving little over the past 30 years. It is clear that continued adaption of current therapies will probably not improve these statistics and, for progress to be made, integration of biology with the design and implementation of future clinical trials is required. Indeed, advances in our understanding of the biology of ALCL are outstripping our ability to clinically translate them; laboratory-based research has highlighted a plethora of potential therapeutic targets but, with high survival rates combined with a scarcity of funding and patients to implement paediatric trials of novel agents, progress is slow. However, advances must be made to reduce the side-effects of intensive chemotherapy regimens whilst maintaining, if not improving, OS and EFS.

Keywords: Children's Oncology Group; European Inter-Group for Childhood non-Hodgkin Lymphoma; anaplastic large cell lymphoma; anaplastic lymphoma kinase; anaplastic lymphoma kinase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase / antagonists & inhibitors
  • Anaplastic Lymphoma Kinase / genetics*
  • Anaplastic Lymphoma Kinase / metabolism*
  • Biomarkers, Tumor
  • Child
  • Combined Modality Therapy
  • Disease Management
  • Humans
  • Lymphoma, Large-Cell, Anaplastic / diagnosis
  • Lymphoma, Large-Cell, Anaplastic / etiology*
  • Lymphoma, Large-Cell, Anaplastic / metabolism*
  • Lymphoma, Large-Cell, Anaplastic / therapy
  • Molecular Targeted Therapy
  • Prognosis
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Translational Research, Biomedical*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • ALK protein, human
  • Anaplastic Lymphoma Kinase