10 December 2018

A new tool has been devised to help identify people who have the most aggressive type of lymphoma and are less likely to respond to standard drugs.

Gene expression profiling demonstrated that one in ten patients with diffuse large B-cell lymphoma were half as likely to have their disease controlled after being treated with the R-CHOP regime.

Diffuse large B-cell lymphoma (DLBCL) affects almost 5,000 people in the UK every year and is the most common form of the disease.

A research team from the Universities of Leeds, Cambridge and Southampton used complex computer models to analyse usage of 20,000 genes of the human genome, and built upon previous work to identify a ‘molecular high-grade’ gene expression signature.

Using data from the REMoDL-B clinical trial, they found that while many people with DLBCL respond positively to existing treatment, people with the molecular high‑grade signature do not respond well to regular treatment.

Patients in this group had a three-year progression-free survival rate after standard treatment of only about 37%, compared to 72% for all other cases.

What’s more, this molecular high-grade group is twice as large as poor-prognosis groups identified by existing methods, such as the ‘double-hit’ group with rearrangements in the MYC and BCL2 and/or BCL6 genes.

Reporting in the Journal of Clinical Oncology, the researchers say their findings should lead to a reassessment in the way that diagnoses are made.

Co-senior author Professor Ming-Qing Du, from the Division of Cellular and Molecular Pathology at the University of Cambridge, said: “By identifying the molecular high-grade group we have found that the number of people who have a high chance of their lymphoma responding poorly to existing treatment is double what we expected.

 “This should be a spur for pathologists to urgently re-assess the way we make the diagnosis, so that appropriate therapy can be tailored to the individual.”

Source: Sha, C., Barrans, S., Cucco, F., Bentley, M.A., Care, M.A., Cummin, T., Kennedy, H., Thompson, J.S., Uddin, R., Worrillow, L., Chalkley, R., van Hoppe, M., Ahmed, S., Maishman, T., Caddy, J., Schuh, A., Mamot, C., Burton, C., Tooze, R., Davies, A., Du, M.-Q., Johnson, P.W.M., Westhead, D.R. (2018) “Molecular High-grade B-Cell Lymphoma: Defining a poor risk group that requires different approaches to therapy”, Journal of Clinical Oncology, available at doi: 10.1200/JCO.18.01314


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