Discover and read the best of Twitter Threads about #Ibrutinib
Most recents (4)
BTK inhibitors have transformed the lives of many patients with Chronic Lymphocytic Leukemia and other lymphomas. These drugs "exploded" onto the scene in 2013-2014 and have fundamentally changed the way we treat the disease. What many people don't know is how it all happened..
In 2004 I became convinced that turning off B-cell receptor signaling would cause cancerous b-cells to stop growing. This theory came into focus based upon an understanding of epstein barr virus protein LMP2A, EBV relationship to Hodgkin lymphoma, and other breadcrumbs
I decided the best way to turn off the receptor would be to use drugs which shut off the signaling pathways emanating from the B cell receptor - notably SYK.
Fortunately Ron Levy M.D. of Stanford was willing to let me test the hypothesis in the laboratory
Fortunately Ron Levy M.D. of Stanford was willing to let me test the hypothesis in the laboratory
Aberrant #glycosylation of anti-Spike antibodies promotes #thrombosis as observed in severely ill #COVID19 patients. Very interesting work from our collaborators in the UK: biorxiv.org/content/10.110…. A few thoughts on why this could be important. 1/4
Severely ill patients make IgG with aberrant glycosylation. We previously showed that this (over)activates lung macrophages, which in turn activates endothelium, which in turn activates platelets. But this paper shows that the antibodies (over)activate platelets directly! 2/4
Interestingly, anti-Spike IgG with “normal” glycosylation (mild COVID-19 patients) has no effect. Only IgG with the combination of low fucose AND high galactose (severely ill patients) promotes thrombosis. In contrast, (over)activation of macrophages only requires low fucose. 3/4
So how safe is #Ibrutinib ?
A very relevant question given that it needs to be administered indefinitely.
41% discontinuation rate in the "real world", most d/t toxicity.
Thread [1/12]
A very relevant question given that it needs to be administered indefinitely.
41% discontinuation rate in the "real world", most d/t toxicity.
Thread [1/12]
So what are the major adverse events anyway ?
1. A fib
2. ⬆️ Risk of bleeding
3. ⬆️ Infections
4. Arthralgias
5. Htn
6. Diarrhoea
7. Pneumonitis
[2/12]
1. A fib
2. ⬆️ Risk of bleeding
3. ⬆️ Infections
4. Arthralgias
5. Htn
6. Diarrhoea
7. Pneumonitis
[2/12]
A very common concern is tox no.1 and 2 .
⬆️A .fib = anticoag for stroke prophylax. but that's when tox no.2 comes into play.
Very difficult to ⚖️ it out .
In RESONATE trial >grade 3 afib in 3% of pts.
Most events occur within 3 mts of starting #ibrutinib
[3/12]
⬆️A .fib = anticoag for stroke prophylax. but that's when tox no.2 comes into play.
Very difficult to ⚖️ it out .
In RESONATE trial >grade 3 afib in 3% of pts.
Most events occur within 3 mts of starting #ibrutinib
[3/12]
Re: #COVID19 / #Hydroxychloroquine - single arm phase 2 data is the scientific equivalent of a hypothesis - don’t confuse larger number of uncontrolled patients as evidence - it is only the volume with which you are yelling. Proof requires randomized studies @VPrasadMDMPH
Sometimes uncontrolled ph2 studies show “preliminary findings” that in the judgement of experts render the “hypothesis” compelling or encouraging, but you still cannot argue that it is proof something works. And yes - the therapy “can still hurt” @realDonaldTrump
Sometimes uncontrolled ph2 studies are even good enough to get a new cancer therapy approved #ibrutinib in cll/mcl but the burden of evidence remains on the Pharma company to perform the correct study and create proof.
