A multicenter phase 1 trial of the immune checkpoint blocker ipilimumab found clinical benefit in nearly half of blood cancer patients who had relapsed following allogeneic stem cell transplantation, according to investigators from Dana-Farber Cancer Institute, who developed and lead the study.
The study reported at the American Society of Hematology annual meeting is the first in which ipilimumab was given in multiple doses over an extended time period, the researchers said.
At a median follow-up time of six months, "We have seen less toxicity than expected and a strong efficacy signal, and that's very encouraging in a population that does not have many therapeutic options," said Matthew S. Davids, MD, MMSc, medical oncologist at Dana-Farber, the first author on the abstract. Robert J. Soiffer, MD, chief of the Division of Hematologic Malignancies at Dana-Farber is the senior author.
The 13 patients in the study had been treated for a variety of hematological cancers and had suffered relapse a median of 19 months following transplant from a related or unrelated donor. Ipilimumab, which blocks the CTLA4 immune checkpoint to augment the patient's immune response to the cancer, was given every three weeks for four induction cycles, then every 12 weeks for up to a year.
Nine patients were discontinued - eight because of disease progression and another who developed chronic graft-versus-host disease (GVHD). Four patients remain on treatment, and the six-month survival rate is 65 percent, the investigators reported.
The preliminary evaluation found that five of 11patients (45.4 percent) who were evaluable for response had clinical benefit. One patient, who had Hodgkin lymphoma, had a near complete response, with dramatic shrinkage of tumors that had spread widely in the bones, and had a complete marrow response after only seven weeks of treatment. Additional partial responses were seen in a patient with multiple myeloma and in a patient with acute myelogenous leukemia. A complete response was seen after just one dose of ipilimumab in a patient with myelodysplastic syndrome. According to the investigators, this represents the first responses to ipilimumab ever observed in patients with myeloid malignancies. The higher of two doses of ipilimumab is currently being given in a phase 1b expansion cohort, and "we've already seen some encouraging results in these patients," Davids commented.
The Cancer Therapy Evaluation Program of the National Cancer Institute sponsors the trial (CTEP 9204, NCT01822509), which is funded in part from an NIH R01to Soiffer (NIH R01 CA183560) and from a grant from the Leukemia & Lymphoma Society Blood Cancer Research Partnership, which helps to facilitate the multicenter component of the trial.