Abstract 2190


Telomerase activity in leukemic blasts is frequently increased in high-risk AML patients, and the major protein catalytic subunit of telomerase (hTERT) includes immunogenic epitopes which can stimulate generation of hTERT-specific cytotoxic T cells.


We evaluated the feasibility, safety, and immunologic effects of telomerase catalytic subunit (hTERT)-expressing autologous dendritic cells (DC) in adult AML patients. GRNVAC1 (VAC1) was produced at a central facility from patient-specific leukapheresis harvests. Immature DCs from monocyte-enriched PBMCs were electroporated with an mRNA construct encoding hTERT and a lysosomal targeting sequence (LAMP-1). Further culture with cytokines induced a mature DC phenotype. AML patients were eligible if in CR1 and with intermediate or high risk cytogenetics or in CR2. PBMCs were harvested after induction, and before or after completion of planned consolidation cycles. Patients in ongoing CR or early relapse (<20% marrow blasts) were vaccinated. Vials of VAC1 containing 1 × 107 cells were administered by intra-dermal injections weekly × 6, followed by 4 weeks off, then as boost vaccinations every other week × 6. In cases where additional vials were available, injections could then continue on a q28 day extended boost schedule. This abstract summarizes safety of administering VAC1 up through the extended boost schedule.


Between September 2007 and December 2009, 33 patients with a median age 61yrs (range, 30–75) were enrolled and leukapheresed. 21 patients received VAC1 vaccinations, 19 in CR (16 in CR1 and 3 in CR2) and 2 in early relapse. Eight of 16 in CR1 were at intermediate risk of relapse and 8 were at high risk of relapse. A median of 17 (6-32) vaccinations were administered to those 19 patients. VAC1 was well tolerated with no toxicities with the exception of one patient who developed ITP after 6 vaccinations. Local transient erythema at the site of injection was common in all patients.

With a median follow-up of 10.5 months (range, 1.2–27.2) months, 4/19 relapsed and 7 continue to receive VAC1. The Kaplan-Meier estimate of disease free survival (DFS) at 12 months, measured from beginning with the first vaccination of VAC1, was 79% for the 19 CR patients (95% CI: 52%-91%), 75% (31%-93%) for the eight patients in the intermediate risk group, and 81% for the 11 patients in the high risk group. Median DFS was not reached.


Prolonged administration of VAC1, up to 32 vaccinations (the maximum number administered so far), is well tolerated in patients with AML, and associated with favorable DFS, especially in high-risk patients.


DiPersio: Genzyme: Honoraria.

Author notes


Asterisk with author names denotes non-ASH members.