General AML

Ipilimumab for patients with relapse after allogeneic transplantation

The anti-CTLA-4 monoclonal antibody, ipilimumab, has been used to effectively improve overall survival in two phase III studies involving patients with advanced melanoma1. Following on from the success in melanoma, Davids M.S, from the Dana-Farber Cancer Institute et al., hypothesized that immune checkpoint blockade, established by targeting CTLA-4 with ipilimumab, may induce a graft-versus-tumor effect in patients with relapse after allogeneic HSCT and lead to a clinical response.2

Davids MS, et al., conducted a phase 1/1b multicenter, open-label, investigator-initiated study to determine the MTD, the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer (12 AML patients out of 28) after allogeneic hematopoietic stem-cell transplantation (HSCT). The results were published in N Engl J Med in July 2016.

The trial was conducted in accordance with the Declaration of Helsinki and ICH-GCP guidelines and was registered at ClinicalTrials.gov (NCT01822509).

The key findings were:

  • No objective response was seen at a dose of 3 mg/kg, whereas 10 mg/kg induced OR in 7 patients out of 22. The 5 CR was observed in patients with extra-medullary AML (4) and in one patient with MDS developing into AML. This patient remained in CR for 16 months.
  • Ipilimumab was active in patients with relapsed hematologic cancers after allogeneic HSCT, but some patients experienced graft versus host disease (GVHD) (2 chronic GVHD of the liver and one case of grade II acute GVHD of the gut) or irAEs (grade 2 immune thrombocytopenia (1), grade 2 pneumonitis (1) and grade 3 colitis and pneumonitis grade 4 (1). This last patient died 42 days after receiving the initial dose of ipilimumab.

These data warrant the further investigation of the use of ipilimumab for patients with relapsed hematologic malignancies after transplantation, however, monitoring for immune-related adverse events is required.

References
  1. Postow M.A, et al. Immune Checkpoint Blockade in Cancer Therapy. J Clin Oncol. 2015 Jun 10;33 (17): 1974–1982. DOI: 10.1200/JCO.2014.59.4358. [Epub 2015 Jan 20].
  2. Davids M.S, et al. Ipilimumab for Patients with Relapse after Allogeneic Transplantation. N Engl J Med. 2016 Jul 14;375 (2):143–153. DOI: 10.1056/NEJMoa1601202.
Download this article:

You can now download this article in Adobe PDF® format.

Download as PDF