IMMU-04. VACCINATING AGAINST NOVEL CYTOMEGALOVIRUS ANTIGENS IN GLIOBLASTOMA USING A PEPTIDE VACCINE IN COMBINATION WITH TEMOZOLOMIDE. (21st September 2021)

• Record Type: Journal Article
• Authors: Hotchkiss, Kelly; Singh, Kirit; Batich, Kristen; Archer, Gerald; Norberg, Pamela; Desjardins, Annick; Friedman, Henry; Johnson, Margaret; Peters, Katherine; Khasraw, Mustafa; Ashley, David; Reap, Elizabeth; Sampson, John
• Is Part Of: Neuro-oncology advances. Volume 3(2021)Supplement 4
• Page Start: iv5
• Page End: iv5
• Publication Date: 2021-09-21
• Subjects: 616.99481
• DOI: 10.1093/noajnl/vdab112.017
• Languages: English
• ISSNs: 2632-2498

Abstract

Abstract: INTRODUCTION: Cytomegalovirus (CMV) antigens are excellent anti-tumor immunotherapeutic targets in glioblastoma (GBM). The PERFORMANCE trial (IRB-pro34208, IND-15846) assessed the feasibility, safety and optimal adjuvant temozolomide (TMZ) regimen to be used with PEP-CMV vaccination in adults with newly-diagnosed GBM. METHODS: Seropositive CMV patients (n=16) were randomized into two arms and treated with standard of care RT-TMZ (SOC) (150-200 mg/m 2 /day on days 1-5 per 28-day cycle) or dose-intensive TMZ (DI) (75-100 mg/m 2 /day on days 1-21 per 28-day cycle). Patients received intradermal PEP-CMV vaccines (500μg of CMVpp65 synthetic long peptide (SLP) mixed with Montanide ISA-51) on days 23, 37 and 51 following TMZ. All patients received tetanus/diphtheria toxoid (Td) preconditioning at the vaccination site on day 22. Serum cytokine levels were measured pre-vaccination, 1-hour and 2-hours post vaccination. PEP-CMV specific circulating PBMCs were quantified at baseline and after each vaccine. RESULTS: Of the 16 trial patients, 7 experienced site-reactions, 4 had grade-II Immune Related Adverse Events (IRAEs), and 4 experienced flu-like grade-III IRAEs. Inflammatory cytokines (IL-2, IFNγ, MIP-1a, IL-8, TNFα, and IL-10) were elevated in patients with grade-III responses 2-hours post vaccine 1. Td p2/p30 specific PBMC levels were similar between IRAEs. However, pp65 responsive PBMCs were elevated at baseline in patients with grade-III reactions compared to site-reaction suggesting pre-existing peptide specific responses may lead to increased vaccine immunogenicity. PBMCs specific for pp65 increased with number of consecutive vaccines. No difference in progression free survival (PFS) or overall survival (OS) was observed between TMZ regimens. CONCLUSION: PEP-CMV vaccination with Td preconditioning is feasible and generates immune responses specific to pp65 in patients with newly diagnosed GBM. Importantly, IRAEs were associated with antitumor efficacy. The mild IRAEs in PERFORMANCE are likely indicative of vaccine potency and can be managed through standard premedication as has been used in other trials with similar IRAEs.