Ipilimumab Appears Active in Relapsed Hematologic Cancer After Allogeneic HSCT

Key Points

  • In patients with relapsed hematologic cancer after allogeneic HSCT who received 10 mg/kg of ipilimumab, response was observed in 32% of patients (compete response in 23%), and tumor regression was seen in 27%.
  • Graft-vs-host disease precluded further treatment in 14% of patients.

In a phase I/Ib study reported in The New England Journal of Medicine, Davids et al found that ipilimumab (Yervoy; at a dose of 10 mg/kg) produced responses, including complete responses, in patients with relapsed hematologic cancer after allogeneic hematopoietic stem cell transplantation (HSCT). It was hypothesized that immune checkpoint blockade via CTLA-4 (cytotoxic T-lymphocyte–associated protein 4) inhibition with ipilimumab could restore antitumor reactivity lost after HSCT via a graft-vs-tumor effect.

Study Details

In the multicenter study, 28 patients with relapsed disease after allogeneic HSCT received induction therapy with ipilimumab at 3 mg/kg (n = 6) or 10 mg/kg (n = 22) every 3 weeks for 4 doses, followed by additional doses every 12 weeks, for up to 60 weeks in those exhibiting clinical benefit.

Responses

No conventional responses were observed in patients who received 3 mg/kg of ipilimumab. Among the 22 patients receiving 10 mg/kg of ipilimumab, 5 (23%) had a complete response, 2 (9%) had a partial response, and 6 (27%) had decreased tumor burden. The complete responses were observed in four patients with extramedullary acute myeloid leukemia and one patient with myelodysplastic syndrome developing into acute myeloid leukemia.

Responses of > 1 year were observed in four patients. Response was associated with in situ infiltration of cytotoxic CD8-positive T cells, decreased activation of regulatory T cells, and expansion of subpopulations of effector T cells in peripheral blood.

Immune-related adverse events, including one death, occurred in six patients (21%), and graft-vs-host disease precluding further ipilimumab treatment occurred in four patients (14%).

The investigators concluded: “Our early-phase data showed that administration of ipilimumab was feasible in patients with recurrent hematologic cancers after allogeneic HSCT, although immune-mediated toxic effects and [graft-vs-host disease] occurred. Durable responses were observed in association with several histologic subtypes of these cancers, including extramedullary acute myeloid leukemia.”

The study was supported by the National Institutes of Health, the National Cancer Institute, the Leukemia and Lymphoma Society Therapy Accelerator Program, Pasquarello Tissue Bank, and Dana-Farber Cancer Institute.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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