Replies to post #475755 on NorthWest Biotherapeutics Inc (NWBO)

[rogers5729]

Well, genuine question: at what point is methylation status tested (and how). Just positing that maybe the fact that non-crossovers are likely to die suddenly or to break off clinical visits for the trial altogether (that is, decide not to crossover), that that is a contributor to poor characterization of meth status. Again, I’m unfamiliar with how that characterization is done, so this could be off base.

[meirluc]

Flipper and GermanCol, wouldn't the trial be facing an ethical dilemma if to fulfill the needs of the trial, a large number of methylated GBM patients and a small number of unmethylated GBM patients were purposely prevented from crossing over?
A roughly equal proportion of methylated and unmethylated GBM patients crossing over would be interpreted as fulfilling the expectation of the trial to give every progressing patient the opportunity to cross over and failure to do so would most likely have been based as an example on a rapid clinical deterioration.
I am sure that every attempt was made to save or at least prolong every patient's life.
To purposely withhold the opportunity of many methylated GBM patients, fewer unmethylated GBM patients or any GBM patient to cross over, seems highly unethical and therefore unlikely to have been carried out. IMHO

[Doc logic]

flipper44,

Trying to remember correctly but I think the earliest group (vanguard) had some of the poorest outcomes and were not identified early on as methylated or unmethylated very well. As I recall the change from Phase 2 to Phase 3 included some of those early patients that were then allowed to cross over but perhaps didn’t make it to that point especially if there was up to a 3 month delay early that was later reduced somehow. Best wishes.

[flipper44]

I’m asking for anybody’s educated opinion on why, in the pool of people that received DCVax-l, only 4.7 percent had unidentified mgmt, whilst 63% of the small group of noncrossovers had unidentified mgmt?

[GermanCol]

I first misunderstood your question.

I'm also trying to understand why. The only thing I can say about that for now is:

- I found the following statemet in the JTM article:

The MGMT gene promoter was methylated in 39.6% of patients (n=131) and unmethylated in 48.9% (n=162), with information not available for 11.5% (n=38; the missing data relates to the early patients enrolled a decade ago)

I think this confirms what you, myself and other people though about the patients with unidentified MGMT gene promoter methylation status being part of the first group of patients.

So, if we take that as a fact, my guess would be that they had technical or logistical issues with crossover at the beginning of the trial when recurrence happened. It would be great if somebody could add something about that in agreement or disagreement.