You have made some important points that should be emphasised: heterogeneity and the not so small detail that DC VAX L may work better in some classifications rather than others but that it does in deed work across all groupings to some extent. It also makes sense that NWBO may not want to reveal which sub-groups respond better to the vaccine because they want broad label approval.
WRT to broad label approval, even if there is some limited benefit for a specific classification, DC VAX L may nevertheless be broadly approved. This is due to the fact of heterogeneity and the personal disease signatures of the particular patient. In such cases, rather than imposing regulatory fiat, it will be left up to the physician and patient to decide. Thus, broad label approval may be more likely particularly for insurance considerations. In a disease like glio stage IV, with very limited alternatives, I would think that the FDA is prescient enough to want to make this therapy broadly available.
Having said all that, and taking into consideration the "inconsistent" MGMT you mentioned and found, if I recall correctly, in the 2018 study, mesenchymal is predominantly M-. What that means precisely is open to question. Does predominantly mean 90%, 80%, 70%, etc.? We don't know. As you point out, mesenchymal could indeed make up about 50% of the stage IV glio population. Studies have shown a broad range up to 50%. I was being very conservative. LL and RP have declared that in their clinical experience, mesenchymal appears to respond much better to the vaccine. It is likely because this strain is highly immunogenic(predominantly) and presents many antigen targets. On the other hand, they found that pro-neural is largely unaffected by the vaccine. Pro-neural appears to predominantly make up the M+ group. but pro-neural makes up less than 20% of the glio stage IV population so you would think that M+ would be significantly smaller than the M- percentage(which conversely would be higher).
Anyway, the 2017 data collection showed a very robust and impressive delta for M+, dependent of course upon the historical control selected and agreed upon by 69 authors. Surely they were aware of various studies even outliers including the 2015 study stating an M+ control of 29 months. Of course, at the time of writing the pub, they were not aware of the small 2018 study where control was indicated at 34 months.
Given LL and RP comments, it is very surprising that M+ has done as well as it has given the pub's control of 21.7 months, since presumably, M+ is composed, predominantly, by the pro-neural grouping. Pro-neural is not nearly as heterogenous as mesenchymal. Accordingly, the historical control used in the pub may no longer be representative. On the other hand, one would think, with the mesenchymal plus Classical grouping which respond better to the vaccine and would constitute more than 50% of the M- population, that M- would do much better than M+. Interesting anomalies IMHO. Hard to figure all this out. Comments anyone?
AI
