Hot Topic the Video Battle of the B cells


The anti CD20 debate

You asked about the slides of ProfB and said you don’t get the nuiance of them. Well in this case, we can help. There were 3 sessions that were live streamed, MD2 was watching. I haven’t seen it yet but will be cringey no doubt, but ProfB had a 15minute slot and got through the slides in about 11-12 minutes. So have a watch and see if you thoughts match what was said.

It is hopefully educational.

It is abit of an info burst

You can also watch the debate too Choose

Hot Topic 6: B-cells in the pathogenesis of MS

However as to the idea that all drugs that work well target the memory B cell population. Here are some pictures from a couple of Posters

Natalizumab they go up as they are trapped in the blood

Henriksen AC et al. Poster 497. Natalizumab selectively reduces plasmablasts in blood. A good example of if you don’t know where to look, you don’t always get the right thing.

As for the others they go down……..Ooops my favourite MS drug didn’t quite make significance..What does that say about my favourite;-(

Kemmerer CL et al. Poster p626 Differential effects of immunomodulating drugs on peripheral blood B cell subsets. NIND non-inflammatory neurological disease and the rest are MS. Rember you are looking at the comparisons to UT (untreated) compared with NAT (natalizumab which goes up, DMF dimethyl fumarate, FTY fingolimod, GLAT glateriamer acetate and IFN interferon Beta)

Also presented was a poster on vitamin D and guess what? A very small effect on memory B cells. Say not more. So here is a prediction the microbiome trials will go the same way. Let’s do a prospective study and see if microbiome drops memory B cells. Pop that in an envelope and put in your time capsule and open it after the 50+ trails that are being done in every country in every disease and the millions of pounds have been spent.

Also I was asked How does oral cladribine work? Well Duh

ProfG had a corporate poster where they showed every cell type and so they don’t put any meaning to specific cells so the message gets lost in what is an easy plausible explanation get trapped into confusion. Too busy making T cell biologists happy.

And just to show it is reprodicible using another technique

Marsh -Wakefield et al. P1225 In depth analysis of B cell in multiple sclerosis patients after treatment with cladribine.The more blue the less of them and so look for the CD27 (forth from the bottom) and just to say I can admit I was wrong. I didn’t think that plasma cells were going to get bashed very much. Looks like I am wrong because the CD138 (second from bottom) population which marks plasma cells is very blue.

Then we have Alemtuzumab

Medina S et al. Poster P990.Lymphocyte changes induces by alemtuzumab in multple sclerosis patients

Finally Ocerlizumab. People has spent their time saying it is T cells and there was an interesting poster suggesting that CD8 CD20 dim cells accumulate in MS lesions. I would say this doesn’t point us towards CD4 Th17 as the EAEers have us believe. But what about the memory B cell. Yep you guessed it

Valasco F et al. Poster p686 Effects of ocrelizumab treatment in peripheral blood leukocytes subsets of Primary progressive multiple sclerosis patients. I added the memory as picture was rather SH1.

Prof Weiner asked about the Specificity and why the Brain? You ask the same question if the talk was about T cells. Why the brain. There must be something specific in the T cell receptor, just like there must be something specific in the B cell receptor.

As for which anti-CD20 to use. Could it be ocrelizumab, rituximab, ofatumumab or ublixumab which were all presented at ECTRIMS2019 I will leave you to watch the debate.

P.S. I wonder who long Ofatumumab will be on the market…..Yep it is available for use in Cancer..not for much longer I now suspect.

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  • Is Cladribine forgotten? Old news? No good? Waste of time? Lately all I hear about is Ocrelizumab so just wondering has Cladribine been thrown on the junk pile?

    • No but I think ocrelizumab is hot cakes. Maybe is people see that it is a chemical B cell depleter that gets in the brain and you don’t have to take forever it may do better. We hope that chariotMS will get the funding all sorted. We.presented on cladribine at ectrims

      • Thanks for replying. My lowest was 0.43 due to start year 2 in january, they’re back at 0.75 at the moment. I would be curious to know if it changes the ocb but could not go through a spinal again

  • So cladribine is effective at depleting both memory b-cells and plasma cells. Gets into the brain and CNS… Isnt this exactly what you would want if the b-cell theory and EVB-hypotysis is true? Looks like a winner, and maybe prof g is right. Maybe its underdosed. All This comes as a suprise to me. Any implications for the new barts trial for add on therapy to clear the plasmacells? If cladribine already does this?

    • Proof is in the Pudding. Merck are doing a study called MAGNIFY where they would have all this data, I’m not sure why they have not reported on this as it is a big study and woul instantly address this properly. The question where the B cells and plasma cells go will be answered. There was a repor inclicating that OCB disappear in about 50% of people within 10 years of treatment….No one piped up so what this was published in claribine last year.

      Again they need to convince people that brain atrophy is affected.

      As for under-dosing. We showed (poster) that there are some individuals who do not deplete in response to cladribine. I suspect there are some super depleters two. THe plasma cell trial is ready to go but not sure if the first person is in.

      • Thank you for responding! And thank you for this blog and your work. I finished my first round of mavenclad in february and my lymph count dropped from 1.2 to 0.5 so maybe im one of those super depleters:)

        • 0.5 is not that low compared to alemtuzumab, which drops to 0.1-0.2 in some people. However the main point with mavenclad treatment is not to drop this count too low. With DrK (should I say SpecialK 🙂 we use lymphocyte numebrs to help guide dosing and we would aim to avoid them going lower than 0.5. Importantly we also think you need to look at cell subsets to get a clearer picture

  • The live broadcast video does not still seem to be accessible or I can’t figure it out. Or maybe you had to have attended the conference ?

    Thanks for the additional graphs and notes in this post.

    If the slides and presentation were not given together in the video, it might be worth making a separate blog post with a refined version in the future. I think a lot of the material may have been touched on in earlier posts if my interpretation is correct. But having it all together in a TED like talk would be a great benefit to all interested in MS research and practice.

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