NorthWest Biotherapeutics Inc (NWBO)

[Doktornolittle]

I started with the belief that TMZ was a bad thing years ago, but have let go of that simple perspective. It does help with the methylated patient population, and it helps a lot.

However, it is not clear to me why it was ever used in the unmethylated population. Further, it seems very likely that the optimum dose of TMZ that should be used when in conjunction with an immunotherapy will prove to be less than when used alone. Flipper recently posted an Italian study pub that concludes that the timing of the combo may be critical. I think Flipper's net net was that you need to stop with TMZ before starting DCVax-L or you damage immune memory.

I don't know if in the past they were able to determine which patients, or patient's tumors were methylated, and I don't know how difficult, or practical that is now. A complication could be in the heterogenous nature of the tumors. Does that include methylation?

But I do know that TMZ damages the immune system in high enough doses. In the past, when used as a monotherapy, it was likely trueley optimum for the methylated patients to use TMZ to the point of severely, even permanently damaging their immune systems, if you assume the patient was not going to live past X years regardless. At least the extra dose slowed the cancer which was more of an imminent threat than the loss of the immune system. Or something like that.

But with the advent of immunotherapies this has to be all re-tweaked. I personally think this should all have been anticipated, and the FDA should have allowed playing with the TMZ regimen in the DCVax-L trials to accommodate these issues, but I don't think that was the case.