gms | German Medical Science

Objective: Recently, a survival benefit of neoadjuvant pembrolizumab (anti-PD-1) treatment in recurrent, surgically resectable glioblastoma (GBM) patients compared to a sole adjuvant anti-PD1 inhibition was shown in a randomized, multi-institutional study and it has been suggested that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response.

Methods: Overall, we analyzed 21 patients (6 f, 15 m) treated with neoadjuvant anti-PD1 inhibition between 03/19 and 12/21. Radiographic response, side effects, hospitalization time, steroid use and progression free survival (PFS), as well as overall survival (OS) were evaluated after neoadjuvant treatment with pembrolizumab therapy and surgical resection and compared to a matched cohort of patients with surgically resectable GBM without additional immune checkpoint blockade treatment. The study was approved by the local ethics committee (PV4904).

Results: The patient cohorts had a median age of 54.35 and 54.67 years respectively. Median time to tumor recurrence (and start of aPD1-treatment) was 12.77 months in the aPD-1 group and 18.70 months in the controls. Mean follow-up period was 22.44 (aPD-1) and 29.53 (ctrl) months. Preliminary comparison of overall survival showed 20.90 (aPD-1) and 29.15 (ctrl) months (p = 0.203, t-test). Survival from time of tumor recurrence was 9.14 (aPD-1) and 10.83 (ctrl) months (p = 0.549, t-test). However, over 50% of patients are still alive in follow-up controls thus further data maturation has to be awaited. Radiographic responses were highly heterogeneous, with some patients indicating immunological flair ups and secondary necrotic transformation with a potential durable response. There was no case of unacceptable toxicity so far.

Conclusion: Neoadjuvant pembrolizumab treatment is feasible in the clinical setting of recurrent GBM patients, however current analyses at this point do not indicate an additional survival benefit in our clinical cohorts when compared to non-ICB treated patients but rather a diverse patter of either durable response or rapid progression, taking into consideration that the anti-PD1 group was already selected for early progression. Further analyses of radiographic responses, treatment success of specific subgroups and long-term follow up data are needed to improve our understanding of the therapeutic efficacy and identify potential subgroups who might benefit from neoadjuvant ICB.