3rd Covid shot while still receiving (O & V)?

[ronsolo306]

I received my Moderna Covid vaccine Jan and Feb 2021 while undergoing treatment for CLL (O & V). No ill effects. I have read that taking and while taking venetoclax greatly reduces the response to the Covid vaccine to only about 15%.

Does anyone have experience taking a 3rd covid vaccine (perhaps J & J) to boost this currently, probably low response? I am still on venetoclax until mid October and my recent flow cytometry results indicate that I am clear of CLL. What a magnificent set of drugs (O & V), but I am concerned about covid. Thanks to all for your thoughts and experiences on this matter. Anyone who has questions or concerns about O & V as treatment for CLL, I will be glad to share my experiences, which are all good.

Thanks again,

Ron

[Robbie_W]

Hi Ron. You pose an interesting question. I have been taking V alone for 3 years and produced only 13 antibodies per mL after getting two Pfizer vaccines. I am considering getting a third shot, probably Moderna in hopes of producing more antibodies. But I know there is not really any data around this. My understanding is that normal folks get 2500 antibodies per mL versus my 13. No i know antibodies are not the only protection offered from the vaccines, but there's no data on T cell response yet...

[gardening-girl]

Ron, when was your last obinutuzumab infusion? It has been reported that individuals who have received CD20 monoclonal antibody treatment within 6 months of vaccination did not produce a measurable antibody response. If your last obinutuxumab infusion was six months ago it might well be beneficial to get a third vaccine dose.

[studebaker in reply to gardening-girl]

How about in reverse situation. Having vaccination before treatment with Obinutuzimab? Would the same 6 months principal apply?Dana

[AussieNeil Partner Administrator in reply to studebaker]

Once you have plasma cells producing antibodies, about 2 to 3 weeks, after vaccination, then the obinutuzumab won't affect them. B-lymphocytes don't express CD20 early and late in their life cycle.

Neil

[studebaker in reply to AussieNeil]

Thank you Neil. I had Rituximab one month after a second Pfizer so as I understand it, there should be some positive response. I am thinking about having antibodies checked now or wait until after I finish Rituximab 🤷🏻‍♀️

Ontario is starting faze 3 opening today, which makes me a bit unsettled. With every opening I have to talk to myself and re-examine my strategy

How to keep safe. Fortunately masking, distancing and hand hygiene is still on here.

Stay safe

Dana

[newyork8 in reply to AussieNeil]

Does the mechanism of Ibrutinib prevent plasma cells from producing antibodies? Has anybody reported response to vaccines while on Ibrutinib? Theoretically even if we had covid the antibody test would not show infection as some of us wont produce antibodies to the infection right?

[AussieNeil Partner Administrator in reply to newyork8]

No, the mechanism of ibrutinib doesn't prevent plasma cells from producing antibodies, but CLL does inhibit plasma cell production - which is why many of us have low antibody production.

See: ncbi.nlm.nih.gov/pmc/articl...

We've also had members reporting antibody production to vaccines while on ibrutinib.

Yes, theoretically, some of us in treatment could have had a COVID-19 infection and not produce antibodies, because our treatment has eliminated all the healthy new B-lymphocytes needed to develop into plasma cells - just as is the case for testing after vaccinations.

Neil

[newyork8 in reply to AussieNeil]

So how do we explain no antibody response for someone MRD negative but on Ibrutinib? If not the Ibrutinib effect then either lasting damage to immune system from past CLL or MRD negative does not mean disease is absent.

[AussieNeil Partner Administrator in reply to newyork8]

First off, plasma cells i.e. mature B-cells, don't tend to be all that much affected by CLL treatments, so existing plasma cells will pretty much continue making whatever antibodies they were making before any CLL treatment.

To make new plasma cells specific to virus causing an infection or a vaccination, you need healthy naive B-cells to go through the selective maturation process to turn into plasma cells making COVID-19 antibodies. If you are uMRD (previously known as MRD negative), then by definition your CLL is undetectable. (About 10% of those on ibrutinib achieve uMRD after four years). Those fortunate enough to have achieved uMRD may also not have any healthy naive B cells, or they may be present, but inhibited by the ibrutinib.

Neil

[newyork8 in reply to AussieNeil]

Yes...inhibited by Ibrutinib....what is that mechanism of action? It inhibits creation of naive B cells? Otherwise why can't the bone marrow produce healthy new B cells. Did CLL permanently damage the production ability. I would add even though uMRD all IGG's subnormal. Why would IGGs stay subnormal if uMRD? Are the IGGs produced by those same B cells that Ibrutinib may be inhibiting? Has anyone that is uMRD and not on treatment recovered their IGGs to normal? Do we have any idea of what % of patients who are uMRD and not on any treatment had a positive antibody response to vaccines? Sorry for the confusion.

[AussieNeil Partner Administrator in reply to newyork8]

Bruton's Tyrosine Kinase (BTK) is an enzyme in the B Cell Receptor pathway and stimulation of this pathway keeps the B cell alive. It's the means by which B cells which are no longer needed to be kept around to fight illnesses are eliminated by apoptosis. BTK inhibitors like ibrutinib, block the keep alive signal so the cells go into apoptosis.

Your bone marrow keeps making B cells - to the extent allowed by bone marrow infiltration by CLL. That infiltration is cleared by treatment, although older chemo treatments can permanently damage the bone marrow and it can take a while for the bone marrow to recover from targeted therapies. Anti-CD20 monoclonal antibodies can keep circulating for up to a year after your last infusion, killing off new B cells. Some of us do see our IgG recover after treatment.

It's too soon to know the answer to your last question.

Neil

[newyork8]

Took 3rd JNJ after 2 Modernas. No antibody response to any but did feel flu-like after JNJ and 2nd Moderna. I am on Ibrutinib and I believe it is blocking perhaps a response.

[ronsolo306 in reply to newyork8]

Thank for your response. How did you go about getting the JNJ, did you just walk into a vaccine site or did you go through a doctor? I have read that some transplant recipients have taken the J&J with great results. That doesn't mean that we will but at least it gives us a chance to be better protected.

[newyork8 in reply to ronsolo306]

I went to a vaccine center and said I was not vaccinated yet. Was able to shop for JNJ. The transplant scenario is different..they don't presumably have an innate issue with their immune system or not taking BTK drug. They take anti rejection drugs.