Real-world observation of personalised peptide vaccines for glioblastoma

Effective and curative therapies for glioblastoma remain elusive. Following standard therapy, a universal recurrence is seen and is associated with limited survival (overall survival (OS) of 15 months).¹ While several novel therapies have been trialled, glioblastoma is still associated with a poor prognosis. Neoantigen-derived personalised peptide vaccines are tailored to individual tumours and have proved promising in the treatment of cancers and are currently being investigated in clinical trials.² Computational prediction is used to identify which neoantigens may be presented on the tumour cell surface. The personalised neoantigen-derived peptide vaccines aim to reduce tumour regression and/or control by T-cell-mediated cytotoxicity, and thus reduce the risk of recurrence. A large real-world observational study investigated the potential of vaccine treatment for patients with glioblastoma.³

Methods

In total, 173 patients with glioblastoma (IDH wildtype) with a median time from diagnosis to vaccine treatment of 10.3 months were enrolled. Of them, 40% received the vaccine treatment prior to progression while the remainder were treated after progression.

Results

At the time of cut-off, 54% of patients were still alive with a median observation time from diagnosis to date of last follow-up or death of 21.3 months. At the time of first vaccination, 92% of patients had received standard of care treatment (radiotherapy and TMZ chemotherapy). The  median OS was 31.9 months. Of note, patients who had received the vaccination prior to progression had a longer OS than those who had progressed (on-treatment OS: 28.9 months vs. 9.8 months, p<0.0001). Adverse events were uncommon and were mainly of grade 1 or 2. A vaccine-induced immune response was noted in 90% of patients, with durable vaccine-specific T-cell responses also being seen. Significantly prolonged predicted OS was also noted for patients with multiple vaccine-induced T-cell responses (53 months vs. 27 months for those with low responses).

Conclusion

This study supports the feasibility of the use of personalised neoantigen-targeting peptide vaccines against glioblastoma.

References

1. Stupp R, et al. N Engl J Med. 2005:352, 987-96.
2. Sellars MC, et al. Cell. 2022: 2770-778.
3. Latzer P, et al. Nat Commun. 2024:15, 6870