A randomized phase II trial of efficacy and safety of the immunotherapy ALECSAT as an adjunct to radiotherapy and temozolomide for newly diagnosed glioblastoma.

Background There is an urgent need for effective treatments against glioblastoma (GBM). In this trial, we investigated the efficacy and safety of an adoptive cell-based immunotherapy. Methods Patients with newly diagnosed GBM were recruited at 4 study sites in Sweden. The patients were randomized 1:2 to receive either radiotherapy (RT), 60 Gy/30 fractions, with concomitant and adjuvant temozolomide (TMZ) only, or RT and TMZ with the addition of Autologous Lymphoid Effector Cells Specific Against Tumor (ALECSAT) in an open-label phase II trial. The primary endpoint was investigator-assessed progression-free survival (PFS). The secondary endpoints were survival and safety of ALECSAT. Results Sixty-two patients were randomized to either standard of care (SOC) with RT and TMZ alone (n = 22) or SOC with ALECSAT (n = 40). Median age was 57 years (range 38-69), 95% of the patients were in good performance status (WHO 0-1). There was no significant difference between the study arms (SOC vs ALECSAT + SOC) in PFS (7.9 vs 7.8 months; hazard ratio [HR] 1.28; 95% confidence interval [CI] 0.70-2.36; P = .42) or in median overall survival (OS) (18.3 vs 19.2 months; HR 1.16, 95% CI 0.58-2.31; P = .67). The treatment groups were balanced in terms of serious adverse events (52.4% vs 52.5%), but adverse events ≥grade 3 were more common in the experimental arm (81.0% vs 92.5%). Conclusion Addition of ALECSAT immunotherapy to standard treatment with radiochemotherapy was well tolerated but did not improve PFS or OS for patients with newly diagnosed GBM.