Ipilumumab Feasible for Recurrent Hematologic Cancers After Allogeneic Stem Cell Transplant
Magnified stem cells
Repeat doses of ipilimumab can restore a complete remission in patients with advanced blood cancers who relapse after allogeneic hematopoietic stem cell transplant (alloHSCT). Approximately one-third of patients with advanced hematologic malignancies will relapse after undergoing the procedure.1
Ipilumumab is an immune checkpoint blocker approved for the treatment of metastatic melanoma. In this study, patients with relapsed hematologic malignancies received ipilimumab in an effort to revive the tumor-fighting powers of the donors' transplanted immune systems. A weakening of the transplanted immune response over time is believed to allow the cancers to recur.
"We believe the donor immune cells are present but can't recognize the tumor cells because of inhibitory signals that disguise them," explained Matthew Davids, MD MMSc, a member of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute, Boston, Massachusetts. "By blocking the checkpoint, you allow the donor cells to see the cancer cells."
Among the 22 patients who were treated with the highest dose of ipilimumab, 5 had a complete response (the cancer was undetectable) and 2 patients had a partial response (tumor shrinkage). Six participants, who did not qualify as having responses, nevertheless had a decrease in their tumor burden. Altogether, ipilimumab therapy reduced cancer in 59% of participants.
The complete responders included 3 patients with a hard-to-treat form of leukemia that affects the skin. These extramedullary myeloid leukemias are not confined to the bone marrow and typically do not respond to standard therapies. They may be particularly sensitive to checkpoint-blocking drugs, the authors noted.
Because checkpoint-blocking drugs such as ipilimumab release the molecular brakes that restrain T cells, a concern was that the treatment could stimulate graft-versus-host disease (GVHD) along with its graft-versus-tumor effect.
"But we didn't see that," said Davids. Only 4 of 28 patients developed GVHD that prevented further treatment, and they all responded to corticosteroid drugs that controlled the GVHD. Six patients experienced adverse effects typical of ipilimumab treatment, and one patient died from an immune-related adverse event.
These encouraging results have led the researchers to plan for larger trials of immune checkpoint blockade in patients with relapsed posttransplant hematologic malignancies. They are also planning studies to determine if immunotherapy drugs could be given to high-risk patients to prevent relapse.
1. Davids MS, Kim HT, Bachireddy P, et al. Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med. 2016;375(2):143-153. doi: 10.1056/NEJMoa1601202.