Abstract 4670: Delayed urticarial reactions in the phase II trial of HER2/neu peptide vaccines + GM-CSF vs. GM-CSF alone in high risk breast cancer patients.
Authors: Trappey Alfred F. , Berry John S. , Vreeland Timothy J. , Hale Diane F. , Sears Alan K. , Clifton Guy , Ponniah Sathibalan , Papamichail Michael , Perez Sonia A. , Mittendorf Elizabeth , Peoples George E. 
Published: August 2014

Abstract
We are conducting a phase II trial evaluating two HER2-specific vaccines (AE37 and GP2) in the adjuvant setting for the prevention of breast cancer (BC) recurrence. We have observed the development of delayed urticarial reactions (DURs) in several patients after inoculation. In this report, we characterize the DURs and analyze immunologic responses (IR) in this population.
After completion of standard of care therapy, disease-free, node-positive or high-risk node-negative BC patients (pts) with any level of HER2 expression (IHC1-3+) were randomized to receive either a peptide+GM-CSF (VG) or GM-CSF (CG). Pts receive 6 monthly intradermal inoculations during the primary vaccine series (PVS) followed by four boosters (B) every 6 mos. IR were measured by local reaction (LR) and delayed type hypersensitivity (DTH) pre (R0) and post-PVS (R6).
Ten (4.3%) of a total 231 initiated pts have had a DUR; 5 in VG (vDUR) (3AE37, 2 GP2), and 5 in CG (cDUR). Median time to onset of symptoms was the same for cDUR/vDUR (median 8 days (d); range, 0-17 d). All DUR pts described generalized pruritis/hives, with two also having difficulty swallowing/globus. Symptoms resolved with IV/oral steroids (n=4), oral steroids only (n=3), or antihistimines (n=3). Duration ranged from 4 d-4 mos with a median of 21 d. vDUR pts had a longer median duration of symptoms than cDUR pts (105 d v 9 d, p=0.02). Four pts (3 vDUR, 1 cDUR) had recurrent symptoms that resolved after treatment similar to above. The majority of events (9) occurred between B1 and B3, but one event did occur after the first inoculation. All DUR pts have received no further inoculations.
Comparing pts who have had a DUR to those who have not (noDUR), there were no significant differences in age, tumor size/grade, HER2 expression, or ER/PR status. 70% of DUR pts have environmental allergies. No other risk factor has been identified. vDUR pts had weaker IR than VG noDUR (LR- R0: 21v36mm, p=0.14; R6: 30v57mm, p=0.17) (DTH - R0: 0.6v2mm, p=0.25; R6: 17v25mm, 0.21). cDUR pts had stronger IR than CG noDUR (LR - R0: 46v1mm, p=0.005; R6: 93v50mm, p=0.01) (DTH - R0: 9.1v2.3mm, p=0.003; R6: 15.3v5mm, p=0.03). There have been no recurrences in the DUR group compared to 11.4% in the noDUR group (p=0.26).
DUR has occurred infrequently with no long-term sequelae. DURs have occurred evenly between vDUR and cDUR indicating GM-CSF is the likely cause. Stronger IR in the cDUR group suggest that these pts's immune system may have a predisposition toward a more robust response to GM-CSF. Less robust DTH/LR as well as longer symptom duration in the vDUR suggest the vaccine may potentiate non-specific systemic immune activation in some pts. We plan to further characterize DUR in our ongoing trial.
Citation Format: Alfred F. Trappey, John S. Berry, Timothy J. Vreeland, Diane F. Hale, Alan K. Sears, Guy Clifton, Sathibalan Ponniah, Michael Papamichail, Sonia A. Perez, Elizabeth Mittendorf, George E. Peoples. Delayed urticarial reactions in the phase II trial of HER2/neu peptide vaccines + GM-CSF vs. GM-CSF alone in high risk breast cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4670. doi:10.1158/1538-7445.AM2013-4670