Editing Dendritic Cell Vaccine (DCVax-L)

{{TreatmentInfo
|drug_name=Dendritic Cell Vaccine (DCVax-L)
|FDA_approval=Under investigation; not yet FDA-approved
|used_for=Glioblastoma Multiforme (GBM), both newly diagnosed and recurrent
|clinical_trial_phase=Phase 3
|common_side_effects=Intracranial edema, nausea, lymph node infection (rare and manageable)
|OS_without=Median overall survival for GBM is typically 15-17 months from diagnosis, or 8 months from recurrence
|OS_with=Median overall survival of 19.3 months from randomization (22.4 months from surgery) for newly diagnosed GBM patients; 13.2 months from relapse for recurrent GBM
|PFS_without=Data not specified
|PFS_with=Median progression-free survival of 6.2 months in the DCVax-L arm, compared to 7.6 months in the placebo group, though this difference was not statistically significant
|usefulness_rating=4
|usefulness_explanation=Shows a clinically meaningful extension of survival in both newly diagnosed and recurrent GBM patients. Offers fresh hope by potentially improving outcomes in a challenging treatment landscape.
|toxicity_level=2
|toxicity_explanation=Well-tolerated with very few serious adverse events related to the treatment, including cases of intracranial edema, nausea, and lymph node infection. No evidence of autoimmune reactions or cytokine storm.
|book_text=Methods to enhance the detection of tumor antigens are now the subject of intensive
research, for various types of cancer. The most successful approach to date involves the
use of dendritic cells, which have been characterized as "professional antigen-presenting
cells". Dendritic cells are extracted from the blood, then co-cultured with a lysate
prepared from cells from the patient's tumor, and stimulated with granulocyte
macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (GM-CSF is the
growth factor used to counteract the decrease in white-cell blood counts due to
chemotherapy). This growth factor causes the mixture of tumor and dendritic cells to be
expanded as well. This mixture is then injected into the patient, evoking an increased
reaction from the immune system.

This use of dendritic cells has been applied to several different types of cancers. Its use
with brain cancer was pioneered by Dr. Keith Black and his team at UCLA, then
continued at Cedars Sinai when Dr. Black’s team moved to that institution. A separate
program at UCLA was continued by Dr. Linda Liau. Other centers using this approach
are in Belgium, China, and Japan. In one of the first small clinical trials (149) nine newly
�diagnosed high-grade glioma patients received three separate vaccinations spaced two
weeks apart. Robust infiltration of T cells was detected in tumor specimens, and median
survival was 455 days (compared to 257 days for a control population). A subsequent
report (150) involving 8 GBM patients produced a median survival time of 133 weeks,
compared to a median survival of 30 weeks of a comparable set of patients receiving
other treatment protocols. At two years 44% of patients were progression free, compared
to only 11% of patients treated with the gold standard of Temodar during radiation and
thereafter. An excellent review of the clinical outcomes and technical issues associated
with the vaccine trials is provided by Wheeler and Black (151).

In the largest of the initial clinical trials (152), 34 GBM patients (23 with recurrent
tumors, 11 newly diagnosed) were assessed for their immunological response to the
vaccine using interferon production as the measure, with the result that only 50% of
patients exhibited a response. The degree of response was moderately correlated with
survival time: 642 days for responders, 430 days for nonresponders. Five of the 34
patients were alive at the time of the report, with survival times ranging from 910 to 1216
days, all of whom were classified as immunological responders. It should be noted that
the average age of patients in this trial was 52 years, only slightly lower than the typical
GBM population, whereas many of the other vaccine trials have included mainly younger
patients.

Among the most promising results using lysate-pulsed dendritic cell vaccines has come
from the UCLA research program led by Dr. Liau. In the most detailed report of the
results (153) 15 newly diagnosed GBM patients and 8 patients with recurrent tumors
(average age =51), received the initial dendritic vaccine (followed by three booster
vaccines in combination with either POLY ICLC or imiquimod (applied locally to the
injection site). For all patients, median time to progression was 15.9 months. Median
survival time for newly diagnosed patients was 35.9 months, and 2- and 3-year survival
rates were 77% and 58%. For recurrent patients, mean survival from the time of initial
enrollment in the trial was 17.9 months. Subsequent reports have come from press
releases from Northwest Biotherapeutics, the biotech company sponsoring the DCVax
trials. Survival at four years has been 33 %, and 27% have exceeded six years (154).
Currently underway is a large multi-center phase III trial.

As of July 2015, no outcomes from the phase 3 DCVax-L trial have yet been made public,
though patient outcomes from an “informational arm” receiving DCVax-L were published
by Northwest Biotherapeutics in March (see press release here). This informational arm
consisted of 51 patients who had enrolled into the phase 3 trial, but were excluded from
the trial due to early disease progression prior to the first vaccination. The patients
received the DCVax injections and were followed up on a Compassionate Use basis.
Survival outcomes in this group are summarized on a youtube video featuring Marnix
Bosch, the company’s Chief Technical Officer. Within this group of 51 patients was a
�subgroup of 25 patients considered to be “indeterminate”, meaning that they had
evidence of disease progression at the baseline visit (rendering them ineligible for the
trial), but subsequently had either stable disease, modest progression, or modest
regression. This group of patients is reported to have a median survival of 21.5 months
(the report does not make clear whether this is from surgery or from randomization
post-radiation). As of March 2015, nine of these patients were still alive after 24 months
of follow-up, six of these nine were alive after 30 months of follow-up, and four of these
nine are alive at 35 to over 40 months. Therefore we can expect that median survival in
the phase 3 trial (patients without disease progression at the baseline visit) will be at least
greater than 21.5 months.
|links=https://www.onclive.com/view/dcvax-l-improves-survival-in-glioblastoma, https://medicalxpress.com/news/2022-11-phase-clinical-trial-brain-cancer.html, https://www.targetedonc.com/view/dcvax-l-extends-survival-in-newly-diagnosed-and-recurrent-gbm
}}