A new treatment approach can benefit cancer patients relapse post-transplant blood -
For many patients of advanced blood cancers, a stem cell transplant may drive the disease into remission. However, about a third of these patients experience a relapse and deal with a very poor prognosis.
But a study from the Dana-Farber Cancer Institute published in New England Journal of Medicine suggests a new treatment approach, using repeated doses of a drug immunotherapy can restore a complete remission for some patients in this difficult situation. This strategy could prevent such relapses in the future.
An immune checkpoint blocking drug approved for metastatic melanoma, ipilimumab was administered to patients with haematological malignancies relapse in an effort to revive the fighting powers of tumor transplanted immune systems donor. A weakening of the immune response transplanted over time is expected to allow cancer recurrence.
The patients received ipilimumab doses ranging repeatedly to one year. ipilimumab blocks an immune checkpoint, CTLA4 that helps cancer cells escape the immune defenses.
"We believe that the donor immune cells are present but can not recognize the tumor cells because of the inhibitory signals that disguise," said Matthew Davids, MD MMSc, a member of the Division hematological malignancies at Dana-Farber and first author of the study. "by blocking the checkpoint, you allow the donor cells to see the cancer cells." Ipilumumab was used primarily in the treatment of advanced melanoma, but in the new study, it has proven effective for cancers of the blood in the post-transplant setting.
A total of 28 relapsed patients with leukemia, lymphoma, multiple myeloma, and myelodysplastic tumors were enrolled in the multicenter Phase 1 trial investigator.
of the 22 patients who were treated with the highest dose of ipilimumab, five had a complete response, meaning the cancer was undetectable and two patients had a partial response, with tumor shrinkage. Six others, who are not considered to have answers, nevertheless had a decrease in tumor burden.
A total ipilimumab therapy reduces cancer in 59 percent of patients relapsed.
Among the complete responders were three patients with hard to treat form of leukemia that affects the skin. These "extramedullary myeloid leukemia," which is not limited to the bone marrow and typically do not respond to standard treatments, may be particularly susceptible to blocking checkpoint drugs, the authors noted.
Because checkpoint-blocking drugs like ipilimumab rev up the immune system by releasing the molecular brakes that limit T cells, it was feared that the treatment could stimulate graft against host disease (GVHD), a complication of serious graft, with its effect of the graft against the tumor.
"But we do not see that," said Davids. Only four of the 28 patients developed GVHD which prevented further processing, and they all responded to corticosteroid medication that controlled GVHD. Six other patients had the typical side effects of ipilimumab treatment, and one patient died of an adverse event related to the immune system.
Investigators said that the encouraging results set the stage for large checkpoint blockade trials in this population of relapse post-transplant patients. Further research is planned to determine whether immunotherapy drugs could be given to high-risk patients to prevent relapse.
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