A major breakthrough in 27 years! Immunotherapy brings the dawn of "new cancer king" treatment!

▎WuXi AppTec content team editor

Glioblastoma is a malignant brain tumor with a very high lethality rate (recurrence rate of nearly 100%), and the clinical prognosis is usually very poor
.
For newly diagnosed glioblastoma patients, the current standard of clinical treatment is surgery, radiotherapy and chemotherapy
.
After initial surgical treatment, glioblastoma patients usually experience recurrence
within 6 to 8 months.
Overall, median overall survival (OS) is about 15 to 17 months, and 5-year survival is typically less than 5%.

From the 5-year survival rate data, glioblastoma ranks in the bottom three among all tumors and is called the "new cancer king"
.

There is currently no standard recommended treatment
for patients with recurrent glioblastoma.
Since 2005, scientists have conducted more than 400 clinical trials in this field (involving more than 32,000 glioblastoma patients), but only one phase 3 trial (TTFields + timozolomide) in patients with newly diagnosed glioblastoma has been shown to provide significant survival benefits, and no phase 3 trials related to recurrent glioblastoma have demonstrated survival benefits
for patients.

Recently, JAMA Oncology published data
from a blockbuster Phase 3 study of the tumor vaccine DCVax-L.
The research paper emphasizes: "This is the first time in 17 years that a Phase 3 study has achieved such remarkable results in the systemic treatment of newly diagnosed glioblastoma patients, and it is also the first time in 27 years that a new treatment has been shown to prolong survival in patients with recurrent glioblastoma
.
"

Screenshot credit: JAMA Oncol.

The current non-randomized, controlled, phase 3 trial evaluated the OS and safety outcomes
of the tumor vaccine DCVax-L in combination with standard therapy for glioblastoma.
DCVax-L is a dendritic cell vaccine that involves drawing blood from the patient, extracting monocytes, differentiating them into dendritic cells, and then "activating" them with a combination of antigens from the
patient's tumor.
The cells are then injected back into the patient, allowing them to recognize and attack the malignancy
.

The study included a total of 331 newly diagnosed glioblastoma patients (aged 18~70 years old)
from 94 medical centers in 4 countries (the United States, Canada, the United Kingdom, and Germany).
Patients were randomized 2:1 to receive DCVax-L+ standard therapy or placebo + standard care
.
Among them, DCVax-L/placebo was administered on days 0, 10, 20, 2, 4, 8, 12, 18, 24, and 30, and the standard treatment was monthly
temozolomide.
All patients with relapse can cross over to or continue with standard treatment with DCVax-L+
.

The primary endpoint was OS from randomization (median 3.
1 months postoperative) in patients with newly diagnosed glioblastoma, and the secondary endpoint was OS
from time of recurrence in patients with recurrent glioblastoma.

The results of the study showed that 232 of the 331 patients were randomly assigned to the DCVax-L treatment group and 99 to the placebo group
.
After tumor recurrence, 64 of the 99 patients in the placebo group crossed over to DCVax-L therapy; Of the 232 patients who have already received DCVax-L, 120 continue to receive DCVax-L
.

• Survival data for newly diagnosed patients:

The median OS of newly diagnosed glioblastoma patients assigned to DCVax-L at enrollment was 19.
3 months (i.
e.
, 22.
4 months before surgery), while the median OS of external control patients from the time of randomization was 16.
5 months (log-rank HR=0.
80; 95%CI=0.
00~0.
94; P=0.
002).

Analytical data showed that patients with newly diagnosed glioblastoma treated with DCVax-L had a relative 20% lower risk of death at any time point, and this relative survival benefit increased over time: 48 months after randomization, DCVax-L and external controls, respectively 15.
7% and 9.
9% of patients were still alive; After 60 months of randomization, 13.
0% and 5.
7% of patients in DCVax-L and external controls, respectively, were still alive
.
Long-term survival patients in studies tend to have good prognostic features
.

• Survival data for relapsed patients:

The median OS of the 64 patients treated with DCVax-L after relapse was 13.
2 months, compared with 7.
8 months for the external control patients (HR=0.
58; 95%CI=0.
00~0.
76; P<0.
001).

Analytical data showed that glioblastoma patients treated with DCVax-L at the time of their first recurrence had a relative 42% lower risk of death at any time point, and this survival benefit persisted over time: 24 months after relapse, 20.
7% in the DCVax-L treatment group and the external control group and 9.
6% of patients were still alive; At 30 months after relapse, 11.
1% of patients in DCVax-L and 5.
1% of patients in the external control group were still alive
.

▲Survival data of patients with recurrent glioblastoma (Image source: Reference [1]).

In terms of safety, DCVax-L is well
tolerated.
A total of 2151 doses of DCVax-L were administered to all patients in the study, and only five serious adverse events were considered at least likely to be treatment-related
.

Overall, the current Phase 3, non-randomized, externally controlled trial found that standard therapy in combination with DCVax-L resulted in clinically significant OS improvements in patients with newly diagnosed glioblastoma and patients with recurrent glioblastoma.

In addition, DCVax-L treatment has an excellent safety profile and a significant long-term survival "tailing effect"
.

The paper highlights that some patients in the DCVax-L group survived for several years after completing the vaccination dose, possibly due to the tumor vaccine DCVax-L bringing effective "immune memory"
to glioblastoma patients.

It is worth noting that DCVax-L therapy can bring a more obvious relative survival benefit than external control groups in some types of glioblastoma patients with poor prognosis under traditional standard therapy (such as elderly patients, patients with a large number of residual tumors after surgery, and recurrent patients).

These encouraging results suggest that the tumor vaccine DCVax-L may play a role
in the broader population of glioblastoma patients.