In the intro to the iHub MB there is a graphic that separates out Methylated(M+) and Unmethylated(M-). The source is an article written in February, 2018 entitled Developments in Molecularly Targeted Agents and Immunotherapies: A Personalised Approach.
These two groups, M+/M-, are then further characterised by molecular sub-groups. M+ is associated with pro-neural and M- is associated with MES, classic and neural. M+ constitutes nearly 40% of the ITT pool (331) and nearly 45% of the categorised group(293 due to the initial 38 patients not being classified.
Further MES is said, by various literature, to constitute any where between 30%~49% of all ndGBM. Accordingly, MES could constitute about 1/2 of the M- group with the other half of classical and neural.
In earlier studies conducted at UCLA, LL/RP found that the vaccine worked particularly well in the MES sub-group which the chart shows as belonging to the M- group. They further noted that the vaccine does little to nothing for the pro-neural group. The chart does not elaborate as to the characteristics of the pro-neural group. For example, is it IDH1 mutant, is it part of the G-cimp methylated grouping. For an additional example, if the pro-neural type does not have IDH1 mutations, it is even more aggressive than the other groups according to an April, 2019 abstract.
The first issue is whether the chart shown in the intro is accurate and can be relied upon to make further analysis given the earlier findings.
Secondly, if it is accurate, it seems to imply, at least if MES is at least predominantly(NF-1 deletion, NF transcriptional error)M-, that the vaccine works quite well in a significant M- population in addition to M+ which according to the chart appears to be all(not predominantly) pro-neural. This would imply that DC VAX works well on perhaps 60%~70% of all ndGBM(M+ and MES in M-). It might also explain the 14.3% survival at 36 months for the M- group due to the assumption(by me) that the MES sub-molecular group may have performed much better in terms of survival at the 36 month milestone but this performance was masked(because we are still blinded) by the performance of the classical/neural sub-molecular group where the vaccine might not performed as well, thus pulling down the overall survival percentage for the overall M- group. In essence, it would appear that DC VAX L works very well on two out of three sub-molecular groups(pro-neural in M+ and MES in M- versus classical in M-. Neural is noted as being de-minimis in recent studies and appears not to be classified as a separate sub-molecular group.
Would be interested in any comments from our more scientifically oriented MB denizens. TIA.
