Preventing cancer relapse with a genetic test

Scientists have found a new way to predict which myeloma patients will benefit the most from a treatment often used to help keep the blood cancer from coming back after a stem cell transplant.

For people with certain high-risk genetic features in their cancer cells, the drug, called lenalidomide, cut their risk of seeing their cancer progress or dying by up to 40-fold. 

The trial, which was run by the University of Leeds’s Clinical Trials Unit in collaboration with the Institute of Cancer Research, London (ICR), suggests that myeloma patients should be genetically tested at diagnosis, so that those most likely to benefit from lenalidomide can be identified – helping tailor treatment to the needs of each patient.  

These interesting findings give us a greater understanding of how genetic testing can be used in cancer research.

The study is published in the journal Blood and was funded by Myeloma UK, Cancer Research UK and the David Forbes-Nixon Foundation. 

Previous research has shown that around one quarter of myeloma patients have various high-risk genetic features. These genetic features can make the cancer more aggressive, less responsive to treatment and likely to relapse more quickly. 

Gordon Cook, Professor of Haematology in Leeds’ School of Medicine, said: "These interesting findings give us a greater understanding of how genetic testing can be used in cancer research, which one day may translate into personalised treatment for multiple myeloma patients." 

Targeted therapy

In this study, ICR researchers analysed data from 566 patients from the Myeloma XI trial, which aims to evaluate the effectiveness of a range of targeted drugs, including lenalidomide, in people with newly diagnosed myeloma. 

Out of the 556 patients on the trial, 17% had so-called ‘double hit’ myeloma (meaning they had two or more high-risk genetic features); 32% had only one high-risk genetic feature, and 51% had no high-risk markers.  

ICR researchers analysed these groups and found that some single-hit myeloma patients benefitted the most from lenalidomide maintenance therapy after a bone marrow transplant – specifically, those with three different genetic abnormalities known as del(1p), del(17p) or t(4;14).  

These patients had an up to 40-fold reduced risk of cancer progression or death, compared to those on observation alone. 

Patients with one of these ’single-hit’ genetic abnormalities lived longer on lenalidomide maintenance therapy – for an average of 57.3 months (almost five years) before their disease progressed, compared to 10.9 months for those on observation alone. 

Those with ‘double hit’ or no high-risk genetic markers also saw some benefit from lenalidomide. They had around a two-fold reduced risk of disease progression or death compared to observation, respectively. However, patients with a different ‘single-hit’ genetic marker known as gain(1q) seemed not to derive consistent benefit from lenalidomide, suggesting this group may be more complex than others.

Patient benefits 

These findings strongly support the use of lenalidomide in myeloma patients who have undergone a stem cell transplant, especially those with single-hit high-risk markers like del(1p), del(17p) or t(4;14) – as well as the use of routine genetic testing in people with myeloma, to identify those most likely to benefit from different treatment strategies.  

Dr Martin Kaiser, Team Leader in Myeloma Molecular Therapy at ICR and Consultant Haematologist at The Royal Marsden NHS Foundation Trust, said: 

“We have found a new way to predict which patients with newly diagnosed myeloma are most likely to benefit from the cancer drug lenalidomide after undergoing a bone marrow transplant.  

“We believe that genetic profiling should be routinely used in myeloma treatment. Knowing which high-risk genetic features are present in each cancer can help us make the best choices when it comes to people’s treatment – ultimately leading to more personalised care.” 

Further information 

Email University of Leeds press officer Lauren Ballinger on l.ballinger@leeds.ac.uk with media enquiries. 

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