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

Katja Werlenius; Giuseppe Stragliotto; Michael Strandeus; Malin Blomstrand; Helena Carén; Asgeir S Jakola; Bertil Rydenhag; Dorte Dyregaard; Karine N Dzhandzhugazyan; Alexei F Kirkin; Martin K Raida; Anja Smits; Sara Kinhult

doi:10.1093/noajnl/vdab156

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

Neurooncol Adv. 2021 Oct 22;3(1):vdab156. doi: 10.1093/noajnl/vdab156. eCollection 2021 Jan-Dec.

Authors

Katja Werlenius^{1

2}, Giuseppe Stragliotto³, Michael Strandeus⁴, Malin Blomstrand^{1

2}, Helena Carén⁵, Asgeir S Jakola⁶, Bertil Rydenhag⁶, Dorte Dyregaard⁷, Karine N Dzhandzhugazyan⁷, Alexei F Kirkin⁷, Martin K Raida⁷, Anja Smits^{8

9}, Sara Kinhult¹⁰

Affiliations

¹ Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
² Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
³ Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
⁴ Department of Oncology, Ryhov Hospital, Jönköping, Sweden.
⁵ Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁶ Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁷ Cytovac A/S, Hørsholm, Denmark.
⁸ Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁹ Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden.
¹⁰ Department of Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden.

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 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.

Keywords: ALECSAT; adoptive cell therapy; glioblastoma; immunotherapy; randomized trial.