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ESMO E-Learning: Double-Hit Lymphomas

Learning objectives

  • To provide a definition of double hit lymphomas
  • To provide essential background on the biology of MYC
  • To elaborate prognostic implications of double hit status
  • To elaborate therapeutic implications of double hit status


This E-Learning module provides an excellent overview of how to define double hit lymphomas, biology of MYC, prognostic and therapeutic implications of double hit status. 

Double hit lymphomas are aggressive lymphomas with MYC and BCL2 or less frequently BCL6 translocations. The author emphasizes that some studies have not even looked for BCL6 translocations and he also underlines that currently the term “double hit” does not refer to lymphomas in which MYC translocations occur with other chromosomal translocations. The term “double hit” implies that these lymphomas harbour only two genetic aberrations. 

MYC is dysregulated in different tumours, including malignant lymphomas. MYC regulates roughly 15% of all genes. It dimerizes with MAX to bind specific DNA sequences known as E-boxes. MYC can activate or repress gene expression. MYC controls different biologic processes. Different genetic aberrations deregulate MYC expression. 

In total 8-10% of all diffuse large B-cell lymphomas (DLBCL) are characterised by MYC translocation. DLBCL with single MYC rearrangement and DLBCL with double hit translocations being characterised by adverse prognosis and inferior survival. The DLBCL patients, who present with double hit status, have an increased risk of relapse in the central nervous system. 

In this E-Learning module, the author elaborates therapeutic implications of double hit status in patients with DLBCL. A special chapter is devoted to the question on whether more intensive regimens are better than treatment with R-CHOP. The author elaborates the evidence from studying dose-adjusted(DA)-EPOCH-R regimen and meta-analysis of dose intensification in double hit lymphomas. 

The author concludes that double hit lymphomas are still not completely defined and understood. MYC-positive and double hit lymphomas seem to be characterised by inferior survival. DA-EPOCH-R regimen might overcome the therapeutic dilemma of MYC-positive and double hit lymphomas. The incorporation of novel agents into molecularly defined subsets of DLBCL is crucial to improve prognosis of affected patients. 

This E-Learning module was published in 2018 and expired in 2020.

Last update: 21 Jun 2018

The author has reported to be conducting research for: Bayer, Celgene, Novartis, Roche, Janssen, AstraZeneca. He is a consultant for: Bayer, Celgene, Novartis, Roche, Janssen, BMS, Hexal, NanoString and Gilead. He has given presentations for Bayer, Celgene and Janssen.

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