06 April 2020

A new drug is showing promise for treating multiple myeloma in the laboratory, paving the way for a drug to be tested in patients, according to a new study.

Researchers at the VU University Medical Centre, Netherlands, have tested the drug, called FL118, in patient samples and mice with multiple myeloma. The drug has already shown positive results when tested on colon and head and neck cancer cells in the lab.

Myeloma is an incurable cancer which 6,000 people in the UK are diagnosed with every year. One mechanism by which myeloma cells become resistant to treatment is through the surrounding healthy cells supporting the cancer.

This new study found that FL118 can still effectively kill multiple myeloma cells when they are surrounded by these support cells, and can even reverse treatment resistance. This suggests the drug could have potential to treat patients that are no longer responding to standard therapies, the researchers write in the journal Haematologica.

The study, led by Dr Tuna Mutis, used samples donated by patients with newly diagnosed or relapsed or refractory myeloma. Interestingly, the team found that FL118 was more effective against cancer cells from patients with advanced disease than the newly diagnosed cases.

FL118 was also found to enhance the effect of melphalan and bortezomib, treatments commonly used for multiple myeloma.

When it was tested in a mouse model of multiple myeloma, the new drug reduced the tumour volume to almost one sixth of its original size, and also delayed tumour growth for up to five weeks.

The research team believes that FL118 could be used in combination with current therapies to overcome treatment resistance. They believe their results suggest it could be effective in relapsed or treatment resistant patients, a group which desperately need new options.

Dr Tuna Mutis said: “The first step towards using this compound in the clinic is to do a phase one trial, which judges the safety of the drug.

“Our collaborators, who also provided this compound, are now planning this trial. In addition to this, we are also testing whether this new drug could improve immune therapy. This would be another important effect, which could demonstrate its usefulness in a wide variety of cancers - not just multiple myeloma.”

The study was part funded by the charity Worldwide Cancer Research. Dr Helen Rippon, chief executive of the charity, said: “The new findings take the first step towards a new drug that could one day be used to treat people with advanced multiple myeloma. As with any new treatment, there is a long journey ahead, but research such as this lays the groundwork for clinical trials in the future.

“Treatment resistance is a huge problem in cancer patients and exciting discovery research like this tackles this issue head on.”

Source: Holthof LC, van der Horst HJ, van Hal-van Veen SE, Ruiter RWJ, Li F, Buijze M, Andersen MN, Yuan H, de Bruijn J, van de Donk NWCJ, Lokhorst HM, Zweegman S, Groen RWJ, Mutis T (2020) “Preclinical evidence for an effective therapeutic activity of FL118, a novel survivin inhibitor, in patients with relapsed/refractory multiple myeloma”, Haematologica, doi: 10.3324/haematol.2018.213314


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