Why Some Patients Do Not Respond To Standard Lymphoma Therapy Discovered

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University of Southampton (England) researchers uncovered clues as to why several patients do not react to the standard drug for the blood cancer lymphoma, increasing optimism that additional effective treatments can be designed.

The study, which was co-funded by the charity Leukaemia & Lymphoma Research, the Medical Research Council, Cancer Research UK and Tenovus, Cardiff is published online in the medical journal Blood.

In the UK, non-Hodgkin’s lymphoma is the sixth most common cancer, causing around 4,500 deaths annually in the country, with increasing cases being reported. Rituximab, which has been the most effective advance in treatment in recent years, works by tagging the surface of the tumorcells so they can be sought out and destroyed by the immune system of the patient.

Professors Mark Cragg, Peter Johnson and Martin Glennie and their teams at the University Of Southampton Faculty Of Medicine are researching explanations as to why an estimated 30% of people, sadly, do not react to treatment.

Researchers discovered that in some patients with lymphoma, after attaching to the surface of the cancer cells, rituximab is quickly internalized inside the cell, meaning the drug does not work as it’s supposed to and immune cells can’t seek out and destroy the cancer cells as efficiently.

Southampton scientists crucially observed, through a string of laboratory tests, that rituximab is internalized increasing faster by the lymphoma cells when a molecule called FcgRLLB is also present at high levels. Investigators discovered in a small preliminary analysis, that patients with high volumes of this molecule were less likely to be treated successfully. To confirm their discoveries, the scientists are proceeding with a larger analysis.

Professor Cragg explained:

“The discovery that high levels of FcgRllb on lymphoma cells can determine how effective rituximab will be could be very significant. It may be that different, non-internalizing antibodies are needed for certain patients. FcgRllb is also a potential target for new drugs to work alongside standard treatments.”

Dr David Grant, Scientific Director at Leukaemia & Lymphoma Research, said:

“Treatment for non-Hodgkin’s lymphoma has made rapid progress but clearly a significant number of patients do not respond to drugs like rituximab. Understanding exactly why they don’t respond is vital so that new drugs can be designed to make sure that every patient survives.”

Dr Ian Lewis, Associate Director of Research at Tenovus reported:

“In addition to helping us devise new drugs and therapeutic strategies for the treatment of lymphoma, this discovery could also help us to identify those patients who will not respond to treatment with rituximab and therefore offer them alternative, more effective treatments at a much earlier stage.”

Leukaemia & Lymphoma Research has £3.7 million currently invested in 15 blood cancer research projects in Southampton.

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