Targeted cancer drug helps lymphoma patients survive
Adding a drug to chemotherapy has helped some patients with an aggressive form of lymphoma live longer.
Southampton researchers Prof Andy Davies and Prof Peter Johnson led the REMoDL-B trial.
They showed they could identify patients with diffuse large B cell lymphoma (DLBCL) most likely to benefit from adding bortezomib to their chemotherapy.
These results could lead to a new treatment option for these patients in the future.
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.
“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.”
The REMoDL-B trial was sponsored by University Hospital Southampton NHS Foundation Trust. It was run by the Cancer Research UK Southampton Clinical Trials Unit.
Over a thousand patients across the UK and Switzerland took part in the trial. Half received standard care R-CHOP therapy. The other half had standard treatment plus bortezomib.
Biopsy samples from participants were also sent to the laboratory for molecular profiling. This allowed the researchers to analyse the genetic make-up of their cancer.
Using genetics to target treatment
The five-year follow-up results show the addition of bortezomib did not improve outcomes for all DLBCL patients. However, 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.”
The REMoDL-B trial was run in collaboration with the Swiss SAKK lymphoma group and the National Cancer Research Institute (NCRI). It was funded by an unrestricted educational grant from Janssen-Cilag and is endorsed by Cancer Research UK.
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. He was a participant on an earlier 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."
Another, similar, trial added a drug called acalabrutinib to standard treatment for people with DLBCL. Positive results have now led to a larger trial, known as REMoDL-A. This is currently recruiting at hospitals across the UK.