Long-term follow-up of patients with acute myelogenous leukemia receiving an autologous telomerase-based dendritic cell vaccine.
ABSTRACT
Background: A phase II clinical trial was conducted in which subjects with AML were administered a telomerase-based dendritic cell immunotherapy (AST-VAC1; hTERT-DCs). The hTERT-DCs were prepared from leukapheresis collections from 33 subjects and were transfected with an mRNA encoding telomerase (hTERT) and the lysosomal sorting signal, LAMP-1, which enhances immunostimulatory activity. hTERT is essential for maintaining the proliferative capacity of tumor cells.
Methods: AML patients were eligible to receive hTERT-DCs if they were in CR1 or CR2 with intermediate or high risk cytogenetics or if they were in early relapse with < 20% marrow blasts. The hTERT-DCs were prepared after induction therapy and before or after completion of consolidation cycles. The hTERT-DCs were administered as 6 weekly followed by 6 biweekly intradermal injections.
Results: Twenty-one patients (median age: 55) in complete remission (16 CR1 and 3 CR2) and or early relapse (2) received at least 3 injections of the hTERT-DCs. Only one grade 3 or 4 adverse event, (idiopathic thrombocytopenia), possibly related to the immunotherapy was observed during the first year. The two patients who were vaccinated during early relapse progressed rapidly and did not receive the full dosing regimen of hTERT-DCs. Of the 19 patients that were in CR, 14 received all 12 doses of hTERT-DCs. Fifty-eight percent (11/19) developed cellular immune responses to hTERT as assessed by peptide ELISpot analysis. Eleven of 19 patients (median follow-up 52 mos.) are still in remission as of last follow-up; seven developed detectable cellular immune responses to hTERT. Of the 19 CR patients, 7 were ≥ 60 yo at the time of hTERT-DC immunotherapy. Four of 7 patients ≥ 60 yo remain relapse free 52-59 months post DC-hTERT immunotherapy with all four developing immune responses to hTERT. The three patients that received DC-hTERT while in CR2 were in remission as of their last follow-up of 24, 50 and 59 months with two having hTERT immune responses.
Conclusions: The results suggest that immunotherapy with hTERT-DCs is safe, can stimulate an immune response to telomerase, and may provide anti-tumor immune responses even in high risk patients with AML Clinical trial information: NCT00510133