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. 2024 Aug 11;15(1):6870.
doi: 10.1038/s41467-024-51315-8.

A real-world observation of patients with glioblastoma treated with a personalized peptide vaccine

Pauline Latzer  1 , Henning Zelba  1 , Florian Battke  2 , Annekathrin Reinhardt  1 , Borong Shao  1 , Oliver Bartsch  1 , Armin Rabsteyn  1 , Johannes Harter  2 , Martin Schulze  1 , Thomas Okech  3 , Alexander Golf  3 , Christina Kyzirakos-Feger  1 , Simone Kayser  1 , Natalia Pieper  1 , Magdalena Feldhahn  2 , Julian Wünsche  1   3 , Christian Seitz  4 , Dirk Hadaschik  5 , Claus Garbe  6 , Till-Karsten Hauser  7 , Christian la Fougère  8 , Dirk Biskup  2 , Dawn Brooke  9 , David Parker  10 , Uwe M Martens  11 , Gerald Illerhaus  12 , Deborah T Blumenthal  13 , Ryan Merrell  14 , Luisa Sánchez Lorenzo  15 , Máté Hidvégi  16 , Paula de Robles  17   18 , Sied Kebir  19 , William W Li  20 , Vincent W Li  20   21 , Matthew Williams  22 , Alexandra M Miller  23 , Santosh Kesari  24 , Michael Castro  25   26 , Annick Desjardins  27 , David M Ashley  27   28 , Henry S Friedman  27 , Patrick Y Wen  29 , Elisabeth C Neil  30 , Fabio M Iwamoto  31 , Bence Sipos  32 , Karsten Geletneky  33 , Lars Zender  34 , Martin Glas  35 , David A Reardon  29 , Saskia Biskup  36   37
Affiliations

A real-world observation of patients with glioblastoma treated with a personalized peptide vaccine

Pauline Latzer et al. Nat Commun. .

Abstract

Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. Tumors from 173 GBM patients are analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. All patients were treated within the scope of an individual healing attempt. Among all vaccinated patients, including 70 treated prior to progression (primary) and 103 treated after progression (recurrent), the median overall survival from first diagnosis is 31.9 months (95% CI: 25.0-36.5). Adverse events are infrequent and are predominantly grade 1 or 2. A vaccine-induced immune response to at least one of the vaccinated peptides is detected in blood samples of 87 of 97 (90%) monitored patients. Vaccine-specific T-cell responses are durable in most patients. Significantly prolonged survival is observed for patients with multiple vaccine-induced T-cell responses (53 months) compared to those with no/low induced responses (27 months; P = 0.03). Altogether, our results highlight that the application of personalized neoantigen-targeting peptide vaccine is feasible and represents a promising potential treatment option for GBM patients.

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Conflict of interest statement

Disclosures for Patrick Y. Wen as research support: Astra Zeneca, Black Diamond, Bristol Meyers Squibb, Celgene, Chimerix, Eli Lily, Erasca, Genentech/Roche, Kazia, MediciNova, Merck, Novartis, Nuvation Bio, Servier, Vascular Biogenics, VBI Vaccines. Disclosures for Patrick Y. Wen as advisory board/consultant: Astra Zeneca, Black Diamond, Celularity, Chimerix, Day One Bio, Genenta, Glaxo Smith Kline, Insightec, Kintara, Merck, Mundipharma, Novartis, Novocure, Prelude Therapeutics, Sapience, Servier, Sagimet, Vascular Biogenics, VBI Vaccines. Conflict of interest for Uwe M. Martens as advisory role: BMS, MSD, Roche, Guardant Health, Sanofi-Aventis, GSK, Novartis. Conflict of interest for Uwe M. Martens as scientific support: Dieter Schwarz Foundation. Saskia Biskup and Dirk Biskup have ownership interests in CeCaVa GmbH and CeGaT GmbH. Dirk Hadaschik is an employee of CeCaVa GmbH. Florian Battke, Johannes Harter, and Magdalena Feldhahn are employed by CeGaT GmbH. Alexander Golf, Julian Wünsche, and Thomas Okech are employed by MVZ Zentrum für ambulante Onkologie GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. No competing interests were disclosed by the other authors.

Figures

Fig. 1
Fig. 1. Survival of patients with stable or progressive disease.
OS (A) and on-treatment survival (B) of patients with either stable (primary; black) or progressive (recurrent; red) disease at the time of personalized peptide vaccine administration (P < 0.0001). Statistical significance of survival differences was computed using the log-rank test. Source data are provided as a Source Data file.
Fig. 2
Fig. 2. OS of patients who received a personalized peptide vaccine (red) in comparison to the matching cohort (publication data, propensity score-matched, black) (P = 0.0032).
Statistical significance of survival differences was computed using the log-rank test. 95% confidence interval of cumulative hazard (log survival) is shown as shaded areas. Source data are provided as a Source Data file.
Fig. 3
Fig. 3. Survival of immunological responders and non-responders and the matching cohort.
A On-treatment survival of immunological responders (iR; black) and non-responders (iNR; red). Significance is given for the comparison between patients with and without positive T-cell response (P = 0.03). B OS of our iR (green, 53.2 months, P < 0.0001 vs publication data) and iNR (red, 27.4 months, P = 0.74 vs publication data) and the matching cohort (publication data) (blue, 22.7 months). C OS of iR (red) and the matching cohort (publication data; black) (P < 0.0001). Statistical significance of survival differences was computed using the log-rank test. 95% confidence interval of cumulative hazard (log survival) is shown as shaded areas. Source data are provided as a Source Data file.
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