276. Long-Term Relapse-Free Survival of Patients with Acute Myeloid Leukemia (AML) Receiving a Telomerase-Engineered Dendritic Cell Immunotherapy

Abstract

There are few treatment options for patients with intermediate and high risk AML, and remission and relapse rates are dismal especially in patients ≥60 years old. A Phase 2 clinical trial was conducted in subjects with AML to assess a dendritic cell immunotherapy (AST-VAC1) engineered to express a modified form of telomerase that is processed through both the MHC Class I and II antigen presentation pathways. AST-VAC1 was prepared from leukapheresis collections from 33 subjects and were transfected with an mRNA encoding near full length telomerase (hTERT) modified with a lysosomal sorting signal, LAMP-1, which enhances presentation to both CD4+ helper and CD8+ cytotoxic T cells. hTERT is essential for maintaining the extended proliferative lifespan of tumor cells. AML patients were enrolled if they were in complete remission (CR1 or CR2) with intermediate or high risk cytogenetics. AST-VAC1 was prepared after induction therapy and before or after completion of consolidation cycles. AST-VAC1 containing 1 × 107 cells was administered as 6 weekly followed by 6 biweekly intradermal injections. If AST-VAC1 doses were available, patients were eligible to receive additional monthly boosts. Twenty one patients (median age: 55) in complete remission (16 CR1 and 3 CR2) or early relapse (2) received at least 3 injections of AST-VAC1. Only one Grade 3 or 4 adverse event, (idiopathic thrombocytopenia), possibly related to the immunotherapy was observed. The majority of adverse events were transient including headache, fatigue, erythema and rash. The two patients who were vaccinated during early relapse progressed rapidly and did not receive the full dosing regimen of AST-VAC1. Of the 19 patients that were in CR, 13 received all 12 doses of AST-VAC1. Fifty-eight percent (11/19) developed T cell immune responses to hTERT as assessed by ELISpot analysis. Eleven of 19 patients (median follow-up 52 mos.) were in remission as of last follow-up; seven developed detectable cellular immune responses to hTERT. Of the 19 CR patients, 7 were ≥ 60 years old at the time of AST-VAC1 immunotherapy. Four of 7 patients ≥ 60 years old remained relapse free 52-59 months post AST-VAC1 immunotherapy with all four developing immune responses to hTERT. The three patients that received AST-VAC1 while in CR2 were in remission as of their last follow-up of 24, 50 and 59 months with two having hTERT immune responses. The median duration of complete remission was greater than that observed in historical controls especially for patients ≥ 60 years old where relapse-free survival at 4 years is typically 5-20%. The results suggest that immunotherapy with AST-VAC1 is safe, can stimulate immune responses to telomerase, and may extend relapse-free survival even in patients with high risk AML.