General AML

Long-term follow-up of AML patients receiving an autologous telomerase-based dendritic cell vaccine

In an article published in Cancer, Hanna J. Khoury from Emory University School of Medicine, Atlanta, Georgia, and colleagues discussed results from their multicenter, open-label phase II study (NCT00510133), which evaluated the safety, feasibility, and efficacy of Human Telomerase Reverse Transcriptase (hTERT)-expressing Autologous Dendritic Cells (hTERT-DCs) vaccine in adult Acute Myeloid Leukemia (AML) patients.

In total, twenty-one patients (median age = 58 years) with intermediate-risk or high-risk AML either in first or second Complete Remission (CR, n = 19) or had early disease recurrence (n =2) received ≥ 3 doses of hTERT-DC vaccine.

The key results of the study were:
  • Grade ≥ 3 Adverse Events (AEs) occurred in 29% (6/21) of patients who received hTERT-DC treatment
  • One patient receiving hTERT-DC vaccine developed a grade 4 idiopathic thrombocytopenic purpura
  • 58% (11/19) of patients receiving hTERT-DC vaccinations at CR developed positive hTERT T-cell response at ≥ 1 time point after administration
  • hTERT specific T-cell responses significantly targeted peptides with low binding affinity for Human Leukocyte Antigen (HLA) compared to peptides with high affinity for HLA
  • At median follow up of 52 months, 58% of patients in CR (11/19) were free from disease recurrence
  • 57% of the patients in CR who were aged ≥ 60 years (4/7) at the time of administration of hTERT-DC vaccine were free of disease recurrence at a median follow-up of 54 months

The authors concluded by stating that “the generation of hTERT-DCs is feasible and vaccination with hTERT-DCs appears to be safe and may be associated with favorable recurrence-free survival” in high-risk patients with AML.

Abstract
BACKGROUND:

Telomerase activity in leukemic blasts frequently is increased among patients with high-risk acute myeloid leukemia (AML). In the current study, the authors evaluated the feasibility, safety, immunogenicity, and therapeutic potential of human telomerase reverse transcriptase (hTERT)-expressing autologous dendritic cells (hTERT-DCs) in adult patients with AML.

METHODS:

hTERT-DCs were produced from patient-specific leukapheresis, electroporated with an mRNA-encoding hTERT and a lysosomal-targeting sequence, and cryopreserved. A total of 22 patients with a median age of 58 years (range, 30-75 years) with intermediate-risk or high-risk AML in first or second complete remission (CR) were enrolled. hTERT-DCs were generated for 24 patients (73%). A median of 17 intradermal vaccinations (range, 6-32 intradermal vaccinations) containing 1×107 cells were administered as 6 weekly injections followed by 6 biweekly injections. A total of 21 patients (16 in first CR, 3 in second CR, and 2 with early disease recurrence) received hTERT-DCs.

RESULTS:

hTERT-DCs were well tolerated with no severe toxicities reported, with the exception of 1 patient who developed idiopathic thrombocytopenic purpura. Of the 19 patients receiving hTERT-DCs in CR, 11 patients (58%) developed hTERT-specific T-cell responses that primarily were targeted toward hTERT peptides with predicted low human leukocyte antigen (HLA)-binding affinities. With a median follow-up of 52 months, 58% of patients in CR (11 of 19 patients) were free of disease recurrence at the time of their last follow-up visit; 57% of the patients who were aged ≥60 years (4 of 7 patients) also were found to be free of disease recurrence at a median follow-up of 54 months.

CONCLUSIONS:

The generation of hTERT-DCs is feasible and vaccination with hTERT-DCs appears to be safe and may be associated with favorable recurrence-free survival.

References
  1. Khoury H.J. et al. Immune responses and long-term disease recurrence status after telomerase-based dendritic cell immunotherapy in patients with acute myeloid leukemia. Cancer. 2017 Apr 14. DOI: 10.1002/cncr.30696. [Epub ahead of print].