Past Vaccines and CLL

[lisakc1]

I am overwhelmed with tears of joy and thanks to all of the people on this forum. I cannot tell you how much your support and responses have helped to relieve our anxiety about the O+V treatment!

At the risk of sounding completely ridiculous, if the O+V wipes out the patient's immune system, ie lymphocytes, then, does it also wipe out any past protection that the patient would have received from vaccines received from childhood on? If not, why? Just trying to understand the science, and many thanks to you all in advance! My husband is completely up to date on vaccines before beginning treatment, just wondering about the futility of it all.

[AussieNeil Partner Administrator]

You and your husband were smart to get him up to date with his vaccinations before he began treatment. Well done!

One of the marvellous things about the drugs developed and approved for CLL treatment, is that by and large, they don't target B cells in their very naive or mature forms. So in general, there's no need to redo vaccinations other than per the schedule for immune compromised folk.

Anti-CD 20 drugs like obinutuzumab, the O in O+V, do keep wiping out new B cells until all the obinutuzumab is used up. That can take at least a year after the last infusion. My B cells started returning 15 months after my last venetoclax and acalabrutinib dose and 22 months after my last obinutuzumab infusion.

Neil

[Poodle2 in reply to AussieNeil]

Neil, what does it mean for you if it takes so long for your B cells to start returning?

I tested my covid antibody levels prior treatment (for reassurance) and they were in the highest range but my CNS said the O+V treatment can change that and might loose my covid antibodies? Does that make sense?

Petra

[AussieNeil Partner Administrator in reply to Poodle2]

With a slow return of B cells, I'm anticipating a long remission, maybe even a cure. I haven't had them tested for any clonality yet.

Few B cells means I'm unlikely to produce much in the way of antibodies in response to vaccinations and infections. My T cell ratio hasn't returned to normal either - CLL often disrupts that. My B cells need to be healthy so that with helper T cell assistance, they'll mature into antibody producing plasma cells and sentinel memory B cells, on the lookout for repeat infections. My immunoglobulin counts are improving, but my IgA and IgM dropped to barely detectable levels during treatment. They were low when I was diagnosed and just kept falling. (I also have weekly subcutaneous IgG).

I think that statement by your CNS is a bit simplistic. This paper goes into how CLL disrupts our immune system and how various treatments vary in their effect on different aspects of our immunity

jeccr.biomedcentral.com/art...

Removing the immune suppressive effect of the CLL tumour burden obviously has to help, but per the paper, we also need our various lymphocyte cells time to recover from the effects of treatment.

On a more practical level, COVID-19 immunity in healthy people needs boosting and seemingly help from more up to date vaccines for the new variants. It's an area where we still have a lot to learn through the US Lymphoma Society study and UK University of Birmingham study on how patients with CLL respond to vaccinations and how their treatment history influences this.

Neil

[Poodle2 in reply to AussieNeil]

Thank you Neil.

[lisakc1 in reply to AussieNeil]

Thank you, Neil! Let me see if I understand. Memory B cells are responsible for immunity from past vaccines. While CLL treatment, O+V destroys some of these cells, it does not target these healthy cells, thereby retaining immunity. However, vaccinations given while undergoing treatment and up to 18 most following the last O infusion, may not be effective as new memory B cells are being generated in that timeframe. I should have taken more biology lol!😀 Also, it appears that B cell memory for current COVID vaccines are short-lived, which to me, makes a stronger case for the anti-body treatment during and after treatment. I'm not a doctor, but that makes sense to me. Thank you again!

[AussieNeil Partner Administrator in reply to lisakc1]

Pretty good summary, only vaccinations and infections give us two types of B cell protection; plasma cells, which make antibodies/immunoglobulins and memory B cells which can last for decades, circulating in our blood. Plasma cells gradually reduce over time, so our antibody production goes down, but if we are exposed to the virus (or other pathogen), the memory B cells quickly transform into plasma cells, again boosting antibody production. We also have a range of T cell protections, including memory T cells.

Neil

[lisakc1 in reply to AussieNeil]

I'm learning so much! Please continue to educate me. This knowledge is invaluable when navigating this disease!

[studebaker in reply to AussieNeil]

This was the best explanation Neil 👍🏻Dana

[SofiaDeo Administrator in reply to AussieNeil]

Yes, great! And re:Covid specifically, some researchers are wondering if T-cells are just as, or even more, important than antibodies. So unless you are doing full traditional chemo, or another treatment that affects T-cells (like my SC Campath did), those parts of your immunity are not known/thought to be greatly affected. It's why these agents are called "targeted treatments"; they are designed to affect specific metabolic pathways, not *kill off everything*. Plus if you are still making immune globulins overall, you generally can fight off infections easier. So monitoring serum proteins/serum albumin gives a general indication of whether or not one is capable of making immune globulins. Some people having problems making immune globulins even with normal serum proteins/albumin, of course, but there will likely be specific symptoms and a doc can test for the various immune globulins if thought necessary.

[jijic in reply to Poodle2]

My B cells were also slow to return and I had no antibody reaction to my first three COVID shots (I have tested positive for antibodies post-infection and second booster).

[craterlake in reply to AussieNeil]

hi Neil , is it the same problem with the rituxamab wiping out B cells as with the O . and is rituxamab and V. as good as the O and V . for treatment of the CLL . thanks as always Neal . james

[AussieNeil Partner Administrator in reply to craterlake]

Obinutuzumab is a second generation anti-CD20 monoclonal antibody, so as hoped by the designers, performs better than rituximab in clinical trials. Like rituximab, it remains in circulation in the blood after the last infusion, continually removing new B cells until it is all used up. That can take at least a year, during which period you won't be able to make antibodies in response to vaccinations or infections.

Sorry to hear of your low platelet challenges.

Neil

[craterlake in reply to AussieNeil]

thanks .