Characteristics of severe adverse events after peptide vaccination for advanced cancer patients: Analysis of 500 cases

Abstract

Abstract. The purpose of this study was to investigate severe adverse events (SAEs) after therapeutic peptide vaccination for advanced cancer patients. We investigated SAEs following personalized peptide vaccinations in 500 advanced cancer patients, including 174 prostate, 74 colon, 51 pancreatic and 43 gastric cancer patients. The number of vaccination cycles varied widely, from 3 to 112. The severity of adverse events was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3, and events with a grade of >3 were defined as SAEs and were evaluated by the Institutional Safety Evaluation Committee. A total of 215 SAEs in 102 patients were recorded during the vaccine trials. The main causes for these events were cancer progression (152 SAEs in 78 patients), combined cancer treatments other than vaccination (35 in 21 patients), diseases other than cancer (20 in 19 patients), peptide vaccines (6 in 6 patients) and suicide (1 in 1 patient). The 6 vaccine-related SAEs, all grade 3, consisted of skin reactions at each injection site, cellulitis around the injection site, edemas of the head and neck regions, colitis, rectal bleeding and bladder-vaginal fistulae. Both cellular and humoral responses to the vaccinated peptides were highly boosted in all 6 of these patients, indicating the involvement of augmented immune responses in these SAEs. The clinical responses in these 6 patients consisted of 2 partial responses and 4 stable diseases. The majority of SAEs after peptide vaccination for advanced cancer patients were caused by cancer progression. The appearance of vaccine-related SAEs, except inflammatory injection site reactions, was unexpected, and fortunately the incidence was very low. Our results suggest that physicians should be on guard for these rare SAEs associated with augmented immune responses.

Vaccine approaches to treat urothelial cancer

“… 55 , 100 Grade 3 or higher AEs are rare, as confirmed in an analysis that described only six severe AEs in 500 patients receiving subcutaneous peptide-based cancer vaccines (1%). 150 These included cellulitis or ulceration around the injection site, edemas of the head and neck regions, diarrhea and rectal bleeding, ulcerative colitis, and bladder-vaginal fistulae. 150 Infrequently, allergic reactions have been reported, mainly mild (rash, itching), exceptionally severe (anaphylaxis).…”

“… 150 These included cellulitis or ulceration around the injection site, edemas of the head and neck regions, diarrhea and rectal bleeding, ulcerative colitis, and bladder-vaginal fistulae. 150 Infrequently, allergic reactions have been reported, mainly mild (rash, itching), exceptionally severe (anaphylaxis). 83 While vaccines are generally perceived as safe, their combination with other therapies, may increase toxicity: rarely, myelotoxicity, increased liver enzymes, acute kidney injury, or urological AEs have been reported, mainly in combination with chemotherapy or ICIs.…”

Beyond Just Peptide Antigens: The Complex World of Peptide-Based Cancer Vaccines

“…Often ACT is combined with other cancer vaccine types, including pulsing DCs with tumour antigen-derived peptides, or transfecting with tumour-associated antigen mRNA (51). The hope of peptidebased cancer vaccines is in bridging the gap between these two alternative strategies by being highly specific, with a low manufacturing cost, and a proven safety record (52). However, challenges remain in improving their immunogenicity and attaining use in the clinic.…”

Towards Personalized Vaccines—Tailoring Peptide Vaccines to Demographic Groups and Individuals

“…Yoshida et al [29] reports from a study of 500 advanced cancer patients The prognosis for pancreatic cancer, however, remains rather bleak.…”