Despite the occurrence of immune-mediate toxic effects and graft-versus-host disease (GVHD), administration of the anti-cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) antibody ipilimumab is feasible for patients with recurrent hematologic malignancies after undergoing allogeneic hematopoietic stem cell transplant (allo-HSCT), according to a study published in The New England Journal of Medicine.
Because the loss of donor-mediated immune antitumor activity following allo-HSCT increases the risk of relapse of blood cancers, researchers assessed whether targeting CTLA-4 with ipilimumab could restore antitumor reactivity via a graft-versus-tumor effect.
For this multicenter, phase 1/1b study, investigators enrolled 28 patients with a relapsed hematologic malignancy after receiving allo-HSCT. All participants received induction therapy with ipilimumab at a dose of 3 or 10 mg/kg every 3 weeks for 4 doses. Patients who had achieved clinical benefit then received additional doses of ipilimumab every 12 weeks for up to 60 weeks.
RELATED: Papular, Nodular Eruptions Frequent With Anti-PD1/PD-L1 Therapy
Among the 22 patients who had received the 10-mg/kg ipilimumab dose, 23% had a complete response, 9% had a partial response, and 27% had decreased tumor burden. Four patients had a durable response for more than 1 year.
Of 28 patients, 21% experienced immune-related adverse events, including 1 death, and 14% reported GVHD that resulted in discontinuation of ipilimumab administration.
- Davids MS, Kim HT, Bachireddy P, et al. Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med. 2016;375:143-153.