Ipilimumab Immunotherapy Treats Relapsed Blood Cancer For Some, Not Others

Ipilimumab Immunotherapy Treats Relapsed Blood Cancer For Some, Not Others

The immunotherapy drug ipilimumab (Yervoy) could stop blood cancer from returning after stem cell transplants in some patients, but a small Phase 1 clinical trial shows that side effects of the treatment could be severe for others.

A report describing the findings, Ipilimumab For Patients With Relapse After Allogeneic Transplantation, published in the New England Journal of Medicine, emphasizes that more research is needed to understand how to best use the drug in relapsed blood cancer patients.

Ipilimumab has been in use for melanoma since approved by the U.S. Food and Drug Administration in 2011. The drug, known as a checkpoint inhibitor, blocks molecules known as immune checkpoints. Cancers often use the checkpoints to evade attack by the immune system. Drugs in this class have been used with success.

In blood cancers, such as lymphoma and leukemia, stem cell transplants can also be used. After a rigorous chemotherapy treatment round wipes out cancer cells and the patient’s own immune cells, patients get a transplant of stem cells from the bone marrow of a healthy donor. The stem cells become new immune cells, protecting the body from infection and making sure the cancer does not come back.

The approach is not always successful; cancers can return. Researchers believe that the explanation for failure might be found in an inability of the new immune cells to launch attacks against the tumor.

In the new study, led by Boston-based Dana-Farber Cancer Institute, researchers tested that the shortcoming could be overcome by the checkpoint blocker ipilimumab.

“We believe the donor immune cells are present, but can’t recognize the tumor cells because of inhibitory signals that disguise them,” Dr. Matthew Davids, first author of the study, said in a news release. “By blocking the checkpoint, you allow the donor cells to see the cancer cells.”

While almost half of the 28 patients included in the study responded to the treatment, with cancer disappearing entirely in five patients, others did not fare so well. One-fifth of the patients had serious side effects, including inflammation of the gut and lungs. One patient died of severe immune-related side effects.

For four patients who developed graft versus host disease in which the transplanted immune cells start attacking the patient’s own tissues, the ipilimumab treatment was stopped. Fearing that the drug could cause more severe complications, researchers decided that those patients could be treated with standard therapy.

Cancer Research UK’s chief clinician Dr. Peter Johnson believes the study was an important step toward answering questions about the drug’s feasibility in relapsed blood cancer patients.

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

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