DCVax-L Passes Phase 3: Will it be the New Standard of Care for Glioblastoma?
We are currently working hard on the development of the Glioblastoma Navigator system but the news deserves immediate publication! Finally some good news! After a long wait, the article reporting the results of the Phase 3 clinical trial NCT00045968 relating to the DCVax®-L vaccine, sponsored by Northwest Biotherapeutics and conducted by Dr., was published in the scientific journal JAMA Oncology: both median and long-term survival significantly increased in both newly diagnosed and recurrent glioblastoma patients.
We talked about it in our recent video conference call with Ted Taylor and explained how it works. As Ted explained to us, the DCVax®-L requires that the patient undergoes Leukapheresis which is a 2-3 hour process in which the dendritic cells are extracted from the blood taken from the patient thanks to centrifuges. Then it requires 2-3 grams of the most recent patient tumor sample frozen and stored at -70°F (-57°C). The tumor is then broken down into its key components using enzymes and becomes autologous tumor lysate which is exposed to dendritic cells which develop antibodies specific to the patient’s specific tumor and learn to recognize it. The dendritic cells are then concentrated and vials are produced and stored in liquid nitrogen. Finally, this new vaccine is given to the patient in specific doses over a specific time frame. The vaccine is injected into the patient’s arm muscle and makes its way to the lymphatic system. Once there, the dendritic cells that have learned to recognize the patient’s glioblastoma interact with the T lymphocytes that multiply and activate the entire immune system to fight the tumor. Now that the immune system can recognize the tumor, it can eliminate it. In case of recurrences, the process can be repeated to target the new version of the patient glioblastoma.
But let’s get to the results. The objective of the research was to investigate whether the addition of DCVax-L, also called murcidencel, to standard of care is able to prolong the survival of patients with glioblastoma. The study compared overall survival (OS) in patients with newly diagnosed glioblastoma (nGBM) and recurrent glioblastoma (rGBM) treated with DCVax-L in addition to the standard of care (SOC) with control patients treated with placebo and SOC. The international multi-center study was conducted at 94 sites in 4 countries from August 2007 to November 2015. Data analysis was conducted from October 2020 to September 2021.
A total of 331 patients were enrolled in the study, of whom 232 were randomly entered into the DCVax-L group and 99 into the placebo group. The median OS (mOS) for the 232 nGBM patients who received DCVax-L was 19.3 (95% CI, 17.5-21.3) months post-treatment (22.4 months post-intervention) compared with 16.5 (95% CI, 16.0-17.5) months after treatment in control patients (HR = 0.80; 98% CI, 0.00-0.94; P = .002). Survival at 48 months post-treatment was 15.7% versus 9.9% of control patients, and at 60 months it was 13.0% versus 5.7% of control patients. For 64 DCVax-L-treated rGBM patients, mOS was 13.2 (95% CI, 9.7-16.8) months from recurrence compared with 7.8 (95% CI, 7.2-8 ,2) months in control patients (HR, 0.58; 98% CI, 0.00 -0.76; P < .001). Survival at 24 and 30 months after recurrence was 20.7% versus 9.6% and 11.1% versus 5.1% in the control group, respectively. In nGBM patients with methylated MGMT (n = 90) using murcidencel, mOS was 30.2 months post-treatment (33 months post-surgery) versus 21.3 months in the control group (HR = 0.74, p = 0.027). The treatment was well tolerated, with only 5 serious adverse events deemed potentially vaccine-related.
In conclusion, the addition of DCVax-L to SOC resulted in a clinically meaningful and statistically significant extension of survival for both nGBM patients and rGBM patients compared to the control group receiving SOC alone. In other words, this treatment prolongs the life of patients by years, not months, with almost no side effects and nothing prevents it from being combined with other treatments, further increasing their effectiveness.
Unfortunately, many centers in the United States, one center in Canada, one in England and one in Germany participated in the clinical trial, but no Italian center. We hope that this innovative treatment will soon become the standard of care and arrive in Italy! We must do everything possible to make this happen! Patients with a glioblastoma don’t have much time and have difficulty understanding why a clinical trial involving hundreds of patients in dozens of centers with verified and published results should be repeated in Europe and Italy before it can be used in the clinical practise!