There is a 35 patient study in 2015 where there is a table showing methylated heterogeneity vis-a-vis unmethylated. I do not have the link handy but it has been mentioned a number of times on the MB. I obtained the link from one of the posts. BTW, in this article, control for the M+ group was 29 months and the blended result from the pub was 34.7 months. Based upon control of 29 months, I calculated a delta for M+ of 8.43 months. This in and of itself is a breakthrough. However, the pub listed a control of 21.7 months. In that case, Tx delta would be off the charts. We do know that mesenchymal is very mutational and possesses a high degree of heterogeneity. Further, mesenchymal is predominantly not methylated. See Abeta links. LL and RP have stated that according to what they have seen, in addition to patients living longer as a whole, mesenchymal patients, in general, respond very well to DC VAX.
As mesenchymal is not generally methylated and does not involve the MGMT genotype, it appears to be additive to methylated which in the pub accounted for 39.6% of the ITT of 331. It is about 42% of the counted M+/M- population taking into consideration the 38 who were not identified as either M= or M-.
Accordingly, and I think conservatively, DC VAX might be very effective on about 50% of nGBM in general and have some effect across other groups.
I note your point about M-. The delta of 7 months to blended from a control of 12.7(19.8 months) is very impressive and may be due in part to the presence of the mesenchymal molecular group. However, this M- group may not produce the same long tail as the M+ group because there are other strains within the M- grouping that are not as responsive. I think this is to be expected considering the complexity of the tumour morphology.
One important takeaway from the links Abeta provided, is the acknowledgement of the weakness of single/few agents therapies in treating GBM with at best rather modest results. These links also demonstrate that there has been relatively little attention paid to DC VAX and its multi-targeting approach. Of course, no mention was made of the pub blended results, as these articles may have been written prior to its release.
So, again, I think the blended pub data is very impressive and the spring refresh 2018 data may be even better especially with those "sticks" on the 2017 graphs moving along to the right. I think LP may be on her way with an unassailable case before the FDA and other RAs and assured approval. I think there is some truth to the notion that the FDA may be biased towards big P, however, if the data is even on a par with the helmet, there will be public outrage if DC VAX is not expeditiously approved. Thanks again to Abeta for the links and these articles give support for what may be inferred from the blended data in the pub. These articles also confirm control at 14.6 months mOS in general for nGBM where M- is less and M+ is more averaging out to that figure. The deltas using just blended data are impressive by themselves.
Finally, another takeaway from these articles is that PFS, as an endpoint, in these studies MAY NOT correlate to OS. FWIW and JMHO.
