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

Abstract

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 four 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 addition of Autologous Lymphoid Effector Cells Specific Against Tumor (ALECSAT) in an open-label phase II trial. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were survival and safety of ALECSAT. Results Sixty-two patients were randomized to either RT and TMZ alone (n=22) or RT and TMZ 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; HR 1.28; 95% CI 0.70, 2.36; P=0.42), or in median overall survival (OS) (18.3 vs. 19.2 months; HR 1.16, 95% CI 0.58, 2.31; P=0.67). 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.

Personalised therapeutic approaches to glioblastoma: A systematic review

“…Overall, there were conflicting survival results for adoptive cell therapies. A randomised open-label phase III trial of intravenous autologous cytokine-induced killer cells in 180 patients reported prolonged PFS but not OS in treated patients (126); a randomised phase II trial of autologous lymphoid effector cells specific against tumour (ALECSAT) in 62 patients found no significant survival difference between treated and control patients (127). A further non-randomised phase I study conducted by Smith et al (128) reported favourable survival in 25 patients treated with autologous cytokine-specific T cells; patients treated before recurrence had significantly improved OS than patients who had progressed.…”

The Recent Research Progress of NF-κB Signaling on the Proliferation, Migration, Invasion, Immune Escape and Drug Resistance of Glioblastoma

“…It can pass through the blood–brain barrier, and its bioavailability is close to 100% [ 3 ]. It has also been used clinically, and can effectively treat newly diagnosed and relapsed glioblastomas and anaplastic astrocytomas, prolong the survival period of patients, and has good safety and tolerance [ 117 ]. However, overall, the efficacy of TMZ does not satisfy the majority of patients.…”