Brigham and Women's Hospital Articles

Oncology Advances January 2017

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Dana-Farber/Brigham and Women's Cancer Center | 3 • Non-Hodgkin Lymphoma – Dr. Davids is a leading National Principal Investigator of the phase 1 multicenter study of venetoclax in adult patients with indolent or aggressive non- Hodgkin lymphoma who have received at least one prior therapy. This study recently completed accrual. 1-877-DFCI-BWH • (1-877-332-4294) For More Information, Consultation and Referral Dana-Farber/Brigham and Women's Cancer Center is easy to access at 1-877-332-4294, Monday through Friday, 8 a.m. to 6 p.m. Matthew S. Davids, MD, MMSc Medical Oncologist, Center for Hematologic Oncology, Dana-Farber/Brigham and Women's Cancer Center Anthony Letai, MD, PhD Medical Oncologist, Center for Hematologic Oncology, Dana-Farber/Brigham and Women's Cancer Center Immunotherapy Benefits Relapsed Stem Cell Transplant Recipients For many patients with advanced blood cancers, a stem-cell transplant can drive the disease into remission. However, about one-third of these patients experience a relapse and face a very poor prognosis. A Dana-Farber/Brigham and Women's Cancer Center study published in the New England Journal of Medi- cine in July suggests that a new treatment approach, using re- peated doses of an immunotherapy drug, can restore a complete remission for some patients in this predicament. The immune checkpoint-blocking drug approved for metasta- tic melanoma, ipilimumab, was given to patients with relapsed hematologic malignancies in an effort to revive the tumor-fight- ing powers of the donors' transplanted immune systems. A weakening of the transplanted immune response over time is believed to allow the cancers to recur. The patients received varying doses of ipilimumab repeatedly for up to one year. "We believe the donor immune cells are present but cannot recognize the tumor cells because of inhibitory signals that disguise them," said Matthew S. Davids, MD, MMSc, a med- ical oncologist in the Center for Hematologic Oncology at Dana-Farber/Brigham and Women's Cancer Center and first author of the study. "By blocking the checkpoint, you allow the donor cells to see the cancer cells." Ipilumumab has been used primarily in treating solid tumors, but in the new study, it proved effective for blood cancers post transplant. A total of 28 patients with relapsed leukemia, lymphoma, mul- tiple myeloma, and myelodysplastic tumors were enrolled in the multicenter phase 1, investigator-initiated trial. Among the 22 patients who were treated with the highest dose of ipili- mumab, five had a complete response, meaning the cancer was undetectable, and two patients had a partial response, with the tumors shrinking. Six others, who did not qualify as having responses, nevertheless had a decrease in their tumor burden. Altogether, ipilimumab therapy reduced cancer in 59 percent of the relapsed patients. Among the complete responders were three patients with a hard-to-treat form of leukemia that affects the skin. Such ex- tramedullary myeloid leukemias, which are not confined to the bone marrow and typically do not respond to standard thera- pies, may be particularly sensitive to checkpoint-blocking drugs, the authors noted. Because checkpoint-blocking drugs like ipilimumab rev up the immune system by releasing molecular brakes that restrain T cells, there was concern that the treatment could stimulate graft-versus-host disease (GVHD), along with its graft-versus- tumor effect. "We did not see that," said Dr. Davids. Only four of 28 patients developed GVHD that prevented further treatment, and they all responded to corticosteroid drugs which controlled the GVHD. Six other patients had adverse effects typical of ipili- mumab treatment, and one patient died from an immune- related adverse event. The investigators said the encouraging results have set the stage for larger trials of checkpoint blockade in this population of relapsed post-transplant patients. Further research is planned to determine whether immunotherapy drugs could be given to high-risk patients to prevent relapse. Senior author of the report is Robert Soiffer, MD, Chief, Center for Hematologic Oncology and Co-Chief, Adult Stem Cell Transplantation Program at Dana-Farber/Brigham and Women's Cancer Center.

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