Replies to post #208892 on NorthWest Biotherapeutics Inc (NWBO)

[marzan]

Thank you longfellow. I think LP et al are also on the same thinking about the ICI + DcVax combo trials and so are delays in kick starting them. LP might have chosen to get the DcVax L approved first. If ICIs are not that of a great therapy as was expected, I think DcVax is going to rule the IO world in the future, imo. All we need is LP to unblind the trial now, imo. Rest will catch up like a jungle fire, imo. Lets see what she got next Wednesday.

[longfellow95]

In fact this is a very interesting statement by the FDA about the increased risk of death associated with adding Keytruda to dexamethasone (a steroid) and lenalidomide or pomalidomide (immune modulators) in the treatment of Multiple Myeloma.
(Dex is also widely used to reduce swelling in GBM.)

https://www.fda.gov/Drugs/DrugSafety/ucm574305.htm

The FDA go on to say:-

This statement does not apply to patients taking KEYTRUDA® (pembrolizumab) for an approved indication. The safety and efficacy of using KEYTRUDA® (pembrolizumab) for approved, on-label uses have been proven. Patients on KEYTRUDA® (pembrolizumab) for an approved use should continue to take their medication as directed by their health care professional.
KEYTRUDA® (pembrolizumab) is currently approved by the FDA for treatment of:

Melanoma
Lung Cancer
Head and Neck Cancer
Classical Hodgkin Lymphoma
Urothelial Carcinoma
Microsatellite Instability-High (MSI-H) Cancer

Not a qualified statement about balance of risk and benefit.
An unqualified statement saying "The safety and efficacy of using KEYTRUDA® (pembrolizumab) for approved, on-label uses have been proven."


When as we know, there is a huge gamut of serious auto-immune toxicities following ICI treatment.

With increasing patient exposure to immunotherapy, the nature and range of irAEs is becoming more clearly defined, and several new but serious adverse events have been reported [22]. Skin, gut, endocrine, lung and musculoskeletal irAEs are relatively common, whereas, cardiovascular, hematologic, renal, neurologic and ophthalmologic irAEs are well-recognized but occur much less frequently (Fig. 1). Although the majority of irAEs are mild to moderate in severity, serious, occasionally life-threatening irAEs (e.g., severe colitis, pneumonitis, encephalitis, toxic epidermal necrolysis, myocarditis, and autoimmune type I diabetes mellitus [T1DM] presenting as diabetic ketoacidosis), are reported in the literature, and treatment-related deaths have been reported in up to 2% of patients in clinical trials [14, 23, 24]. As life-threatening irAEs are rare, and may mimic other better-known conditions, there is growing recognition of the need to educate both the oncology and general medical communities in recognizing and instituting urgent and appropriate treatment of these conditions.

https://jitc.biomedcentral.com/articles/10.1186/s40425-017-0300-z


Not my idea of 'safe'.

Then there is the study of ICI use in Head and Neck which reported a 29% rate of hyper-progressive disease associated with ICI's leading to rapidly accelerated disease and death.

https://www.ncbi.nlm.nih.gov/pubmed/28419181


Definitely not my idea of 'safe'.

[CogDiss 1188X]

Agree with your thoughts on chemo — unfortunately it is still widely used and most likely will continue to be for quite awhile. Obviously wish it worked better for more people. Regarding ICIs, it is still early days and much to learn about risk/benefits and best use. Certainly would consider it (and chemo for that matter) if it were applicable to a particular cancer I happened to have, but it’s a gift horse whose mouth I would scrunitize as well as I could.

Efficacious, well-tolerated. Reminds me of a quote from The Princess Bride:

“You keep using that word. I do not think it means what you think it means." — Inigo Montoya