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. The study was reported at the 56th annual meeting of the American Society of Hematology in San Francisco, California.

The study was developed and led by researchers from Dana-Farber Cancer Institute in Boston, Massachusetts. It is the first in which ipilimumab was given in multiple doses over an extended time period, the researchers explained.

At a median follow-up of 6 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 first author Matthew S. Davids, MD, MMSc, medical oncologist at Dana-Farber. Robert J. Soiffer, MD, chief of the Division of Hematologic Malignancies at Dana-Farber is the senior author. 

Continue Reading

The 13 patients in the study had been treated for a variety of hematologic 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 3 weeks for four induction cycles, then every 12 weeks for up to 1 year. 

Nine patients were discontinued, including eight because of disease progression and another who developed chronic graft-versus-host disease (GVHD). Four patients remain on treatment, and the 6-month survival rate is 65%, the investigators reported. 

The preliminary evaluation found that 5 of 11 patients (45.4%) 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 7 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 R01 to 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.