Immunotherapy Shows Promise Treating Blood Cancers


Patients who relapse following a stem cell transplant for leukemia, lymphoma, or multiple myeloma may benefit from ipilimumab.

Stem cell transplants have proven beneficial in patients with advanced blood cancers by helping them achieve remission, but there is still approximately one-third of patients who relapse and face a very poor prognosis. However, a new treatment approach that involves repeated doses of an immunotherapy drug can help restore complete remission in this proportion of patients.

In a study published in the New England Journal of Medicine, researchers found that the immune checkpoint CTLA4-blocking drug ipilimumab, which was previously approved for metastatic melanoma, helped some patients with relapsed hematologic malignancies achieve complete remission.

A total of 28 patients with relapsed leukemia, lymphoma, multiple myeloma, and myelodysplastic tumors were enrolled in the multicenter, phase 1 trial. Participants were repeatedly administered varying doses of ipilimumab for up to a year.

The results of the study showed that of the 22 patients treated with the highest dose of ipilimumab, 5 achieved a complete response, and 2 had a partial response. Although there were 6 patients who did not qualify as having a response, they did experience a decrease in tumor burden.

Overall, the ipilimumab therapy reduced cancer in 59% of the relapsed participants.

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

In the group of patients who had a complete response, 3 had a hard-to-treat form of leukemia that affects the skin. These extramedullary myeloid leukemias typically do not respond to standard therapies and are not confined to the bone marrow. Authors noted that this form of leukemia may be particularly sensitive to the checkpoint-blocking drugs.

During the study, researchers were concerned that the treatment could stimulate graft-versus-host disease (GVHD) along with its graft-versus-tumor effect, because checkpoint-blocking drugs stimulate the immune system by releasing molecular brakes that restrain T cells.

“But we didn’t see that,” Davids added.

There were only 4 out of 28 patients who ended up developing GVHD that prevented further treatment. However, all 4 patients responded to the corticosteroid drugs that controlled the GVHD.

Six other patients had common ipilimumab-induced adverse effects, and 1 patient died from an immune-related adverse event. Authors noted that the findings will set the stage for larger trials of checkpoint blockade drugs in this population of patients.

Furthermore, researchers plan to conduct additional research to determine if immunotherapy drugs could be used on high-risk patients to prevent relapse.

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