Certain genetic faults could help predict success of immunotherapy

A certain group of genetic faults could be used to help predict if immunotherapy will work in cancer patients, according to a new US study.

The research from John Hopkins University in Baltimore found that a significant number of patients whose tumours had defects in genes involved in DNA repair responded to the immunotherapy drug, pembrolizumab (Keytruda).

The researchers looked at the genes in patients’ tumours. They found that the patients who responded to this treatment all had cancers with defects in a set of genes called mismatch repair genes.

Previous studies have looked at colorectal cancer but this trial, involving 86 people, studied 12 different types of cancer, suggesting pembrolizumab or similar drugs could be used against multiple cancer types.

Clinical tests for these genetic defects are widely available, so this could one day help doctors determine if immunotherapy is the best option for a patient before they start treatment.

Dr Edd James from the University of Southampton and a Cancer Research UK expert in cancer immunology said: “These results are interesting because patients who had tumours with these genetic faults responded well to immunotherapy treatment.”

The results, published in Science, showed pembrolizumab controlled the disease for 66 patients, with tumours completely disappearing in 18.

While the trial is still ongoing, 11 patients have now stopped receiving the therapy and remained disease-free, with no evidence of their cancer coming back.

Pembrolizumab targets and blocks a protein called PD-1 on the surface of certain immune cells called T-cells. Blocking the PD-1 protein triggers the T-cells to find and kill cancer cells.   

The drug is currently approved for only a few types of cancer cases.

James said this study adds to previous evidence that defects in mismatch repair genes could be a good indicator of a patient’s response to immunotherapy drugs and that “faults in these DNA repair genes, could help clinicians identify patients who would benefit most from this type of treatment.”

But he added, “These patients now need to be monitored to see if the effects are long lasting.”

Yet, James says that it is not yet certain whether using these genetic faults as an indicator that immunotherapy would work is suitable.

“A significant number of patients didn’t benefit from the treatment so we need more work to see whether these genetic markers are reliable predictors.”