Trial identifies types of aggressive lymphoma where survival is improved by a targeted cancer drug

Improving current treatments

Currently patients with DLBCL are treated with a combination of chemotherapy and immunotherapy, called R-CHOP.

“Although this treatment works for many people, there are some patients whose lymphoma does not respond to R-CHOP or comes back after initial treatment,” says Professor Davies, Professor of Haematological Oncology at the University of Southampton, who presented the results at the conference earlier.

“Bortezomib is a drug which interferes with the growth of cancer cells. It’s already used in myeloma and mantle cell lymphoma, and we wanted to test if it could also be used to treat people with DLBCL by adding it to their standard treatment.”

Over a thousand patients across the UK and Switzerland were recruited into the REMoDL-B trial. Half were treated with standard care R-CHOP therapy, while the other half were given the standard treatment plus bortezomib. Biopsy samples from participants were also sent to the laboratory for molecular profiling, to analyse the genetic make-up of their cancer.

The five-year follow-up results show that although the addition of bortezomib did not improve outcomes for all DLBCL patients, there were some subgroups of patients with particular genetic markers that did see positive effects.

“For patients with subtypes called Molecular High-Grade (MHG) lymphoma and Activated B Cell (ABC) lymphoma, we saw a reduced risk of the cancer progressing or coming back with the addition of bortezomib,” says Louise Stanton, Principal Statistician at the Southampton Clinical Trials Unit. “Excitingly, we also saw an improvement in the number of patients surviving, and their duration of survival in the ABC subgroup compared to those not given bortezomib.”

Hopes for the future

“These are extremely promising results,” says Professor Davies. “However, bortezomib is not currently licensed or funded for use in patients with DLBCL. The type of molecular profiling that we carried out in the trial to establish these patient subgroups is not routinely carried out on the NHS. But we hope the results from the REMoDL-B trial could lead to the use of more molecular testing in future and new treatment options for these patient groups.”

Richard Stephens was diagnosed with lymphoma in 1998 and was himself a participant on an earlier clinical trial. He worked with the trial team as a patient representative throughout the REMoDL-B trial.

"This study is another step forwards in precision medicine for patients like me, finding the right diagnosis and the right treatment for each of one of us”, says Richard. “I am proud to have been involved in a research project that has produced useful results to improve clinical practice and decision-making."

The REMoDL-B trial was run in collaboration with the National Cancer Research Institute (NCRI) and the Swiss Group for Clinical Cancer Research (SAKK). It was funded by an unrestricted educational grant from Janssen-Cilag and is endorsed by Cancer Research UK.

Advancing our lymphoma research

The long-term results of another lymphoma trial called ACCEPT were also presented at the ASH conference by Professor Davies and the Southampton Clinical Trials Unit team.

Like REMoDL-B, this trial looked at the addition of an extra drug to standard R-CHOP treatment for people with DLBCL. In this trial, it was a drug called acalabrutinib which works by blocking the chemical messages that tell cancer cells to grow.

ACCEPT was a small, early-phase trial that looked primarily at the safety of the drug and aimed to establish the optimum dose of acalabrutinib to give to DLBCL patients.

The results of this trial have led to a larger, phase II trial of acalabrutinib called REMoDL-A which is currently recruiting at hospitals across the UK.