Immunotherapy drugs show promise in a range of advanced blood cancers

People whose blood cancer has returned after a stem-cell transplant could benefit from immunotherapy treatment, according to a preliminary US trial.

The drug, ipilimumab (Yervoy), has been approved for treating lung cancer and melanoma. The latest trial, published in the New England Journal of Medicine, is the first to examine its use in advanced blood cancers.

But while two-thirds of the 28 patients on the trial responded – some extremely well – others had severe side effects and one died, leading to warnings that further study would be needed before the treatments could be used routinely.

Stem-cell transplants are effective treatments for blood cancers such as leukaemias and lymphomas. They replace the patient’s immune system, allowing the donor cells to attack their cancer and can produce long-lasting remissions.

But some patients can relapse, after which there are few effective treatment options.

“These patients tend to be very unwell, and at the moment we have few treatment options to help them”, said Cancer Research UK’s chief clinician, Professor Peter Johnson.

The new study, led by researchers at the Dana-Farber Cancer Institute in the US, aimed to test whether ipilimumab was safe and effective in these patients. 

Ipilimumab works by blocking signals called ‘checkpoints’ that cancer cells subvert, allowing them to hide from the immune system. 

In patients who’ve had stem cell transplants but subsequently relapsed, it’s thought that the drug could allow the transplanted immune cells to re-target the cancer.

“We believe the donor immune cells are present, but can’t recognize the tumour cells because of inhibitory signals that disguise them,” said study leader Dr Matthew Davids, at Dana-Farber and first author of the study. “By blocking the checkpoint, you allow the donor cells to see the cancer cells.”

Of the 22 patients treated with the highest dose of ipilimumab, the cancer completely disappeared in 5 (known as a ‘complete response’), while two others saw their tumours significantly shrink. In total, 13 of the patients had some form of response.

But a fifth of the patients had serious side effects, including a severe inflammatory bowel condition (colitis) and lung inflammation (pneumonitis). And one patient died of an immune-related side effect.

A key concern, however, was the occurrence of serious episodes of so-called ‘graft-vs-host-disease’ (GVHD), where the patient’s transplanted immune system turns on the patient’s own tissues.

“But we didn’t see that,” said Davids. Of the four of 28 patients who developed GVHD that prevented further treatment, all responded to drugs to bring it under control.

Cancer Research UK’s Professor Johnson said it was “an important area of research”, which was starting to answer the question of whether ipilimumab could be safely used to treat relapsing patients.

“However, these results confirmed what many have suspected – that these drugs can cause some serious immune-related side-effects in these patients, and will need to be handled with care.”

“But on the positive side, others appear to have done well –  so while it’s clear that there’s more to do to fully understand how best to use these drugs, it looks like we have an exciting new weapon in our armoury to help people who really need it.”