Yet another misleading article bashing DCVax and immunotherapy, in “The Oncologist,” which not surprisingly, notes this about the DCVax trial:
“These data should be interpreted with caution considering the high crossover rate, the statistical design, and the absence of information regarding the stated primary endpoint of the study which was PFS,”
and concludes,
“the role of immunotherapy in GBM remains a challenge,”
Not surprising, because Novocure is listed in the “conflict of interest” by multiple authors multiple times. (I will give them credit for disclosing it though)
Autologous Vaccines In the context of autologous vaccines as a possible treatment in patients with GBM, there are several early-phase studies in the literature that have evaluated the use of vaccines based on dendritic cells (DCs).78,79 These cells have the task of presenting antigens to naïve T cells to ensure the activation of an adaptive immune response. DCVax-L is the most studied DC vaccine to date, composed of autologous dendritic cells pulsed with autologous tumor lysate that was evaluated in a phase III study in newly diagnosed GBM patients, in combination with maintenance temozolomide after surgery and combined chemoradiotherapy.80 Patients were randomized 2:1 to receive DCVax-L plus temozolomide vs Placebo plus temozolomide; in case of disease progression/relapse during treatment, crossover was allowed. For the intent-to-treat (ITT) population of 331 patients, the mOS was 23.1 months (evaluated from the date of surgery). Due to the possibility of crossover, approximately 90% of all patients in the ITT population received DCVax-L during the study. Treatment was well tolerated with only 2.1% of patients reporting grade 3-4 adverse events possibly related to vaccine treatment. These data should be interpreted with caution considering the high crossover rate, the statistical design, and the absence of information regarding the stated primary endpoint of the study which was PFS.75 A phase III randomized open-label study (NCT04277221)81 is evaluating the use of Autologous Dendritic Cell/Tumor Antigen (ADCTA) immunotherapy in combination with a standard treatment (bevacizumab) in patients with first recurrence of GBM after the Stupp protocol. The primary endpoint was OS whereas the secondary endpoints were PFS, 6-month PFS, and 1- and 2-year survival rates. Another active but not currently recruiting phase II/III study (NCT03548571)82 is evaluating the use of dendritic cell immunotherapy against cancer stem cells in newly diagnosed IDH-wt, MGMT-promoter methylated GBM patients receiving concomitant radiochemotherapy with temozolomide as first-line treatment. The primary endpoint is PFS, whereas secondary endpoints include OS, assessment of patient-reported quality of life, immunological response by analysis of delayed type hypersensitivity reaction in skin and lymphocyte clonal analysis, and safety
Conclusions Immunotherapy is clearly a revolution in the treatment of solid tumors. However, the role of immunotherapy in GBM remains a challenge because of the immunosuppressive nature of this tumor and its unique immune environment. Further studies will be needed to better understand possible strategies to overcome the mechanisms of immunosuppression. Data from clinical trials will show the future path, likely combination strategies may play a role.
Conflict of Interest M.C. declares consulting from Health4U. M.P. declares consulting fromNovocure and Health4U. A.I, reports research grants from Carthera, Transgene, Sanofi, Nutritheragene; travel funding from Enterome and Carthera; personal fees for advisory board from Leo Pharma, Novocure, Novartis, and Boehringer Ingelheim outside the submitted work. G.L. declares consulting or advisory role funding from ABBVIE, Bayer, Novartis, Orbus Therapeutics, BrainFarm, Celgene, CureTeq, Health4U, Braun, Janssen, BioRegio Stern, Servier, Novocure, and travel funding from Roche and Bayer.The other authors declare no financial relationships.
