NorthWest Biotherapeutics Inc (NWBO)

[DJPele]

MUST READ

"Assessment of Treatment Response to Dendritic Cell Vaccine in Patients with Glioblastoma using a Multiparametric MRI-Based Prediction Model"

https://www.researchsquare.com/article/rs-2591941/v1


Below, BIO99's excellent overview of this new journal publication regarding DCVax-L:

"Thoughts on the latest $NWBO DCVax
manuscript preprint (de Godoy et al)
Due diligence:

I read today a preprint of a manuscript by de Godoy et al that was submitted on February 15, 2023 to the Journal of Neuro-Oncology entitled "Assessment of Treatment
Response to Dendritic Cell Vaccine in Patients with Glioblastoma using a Multiparametric MRI-Based
Prediction Model". Remarkably and signifying the importance and urgency of this study to the neuro-oncology community, by February 18, an editor had already been identified, reviewers requested anc
accepted. The preprint can be found at this link: https:/www.researchsquare.com/article/rs-2591941/v1

My thoughts are below.

This paper is significant because the neuro-oncology community has had a difficult time identifying with reliability using non-invasive methods whether someone
is truly progressing (TP) or pseudoprogressing (PSP). i.e., responding to the immunotherapy treatment but looking like they are progressing on MRI. This has been a major hindrance for glioblastoma clinical trials and immunotherapy clinical trials in general. And now there
is a way to do so.

It reliably shows that one can, using multiparametric MRI distinguish between the two, and does so using the gold standard of histopathology. This is a very
important step in reliably monitoring of large numbers of patients receiving DCVax in the future and making decisions on their treatment plan.

This is critical data not just for the FDA and other regulatory agencies to feel even more confident in the utility of DCVax, because they can see correlation between DCVax treatment, pseudoprogression via
MRI and the histology of dead and dying tumors. The histology figure in Figure 1B-F is incredibly striking, showing how DCVax has resutted in death of the whole tumor. Note that the numbering of the panels in Figure 1
is rather unconventional, and I would suggest revision of the numbering system to the authors, if they happened to ever read this.

The correlation between MGMT methylation
Ki67, overall survival, and other factors is striking and interesting. it lends further confidence to the conclusions of the JAMA Oncology paper. The Kaplan-Meier (survival) curves in Figure 2 are a hing of beauty. Amazing stuff. And it's quite logical that
urvival is better if Ki67 levels are lower (remember tha it's a proliferation marker).

It also points to a published animal model study of DCVax that I was unaware of (reference 6)., which I wil look at in my spare time.

I love this sentence: "The improvement in survival in MGMT methylated patients treated with DCVax-L could be due to synergies with TMZ chemotherapy [9]."
pecause it suggests that DCVax even synergizes with chemotherapy.

Overal, this study makes the case that one can reliably identify pseudoprogression using a more advanced MRI technique and shows beautiful and convincing correlations between things that matter to neuroradiologists and neuropathologists, who not only play important roles in regulatory agencies and ADCOMs but also play countless critical roles including
in diagnosis, determination of progression or prognosis treatment decisions, tumor boards, etc.

I'm interested in reading your thoughts on the study in the comments below."

https://www.reddit.com/r/NWBO/comments/117mc29/thoughts_on_the_latest_nwbo_dcvax_manuscript/?utm_source=share&utm_medium=android_app&utm_name=androidcss&utm_term=1&utm_content=share_button