CLL and mRNA Vaccines

[BWHR]

Just saw this abstract, which is one of the papers being presented at the Boston CLL conference:

journals.plos.org/plosmedic...

I don't understand most of it, but this is one of the "Findings":

CLL patients and other immunocompromised populations may benefit from alternative vaccine regimens, which should be evaluated in clinical trials.

Does this mean Novavax might be a better choice?

[AussieNeil Partner Administrator]

That's a great paper, containing further information on the importance of our T cells for our adaptive (B and T lymphocyte based) immunity. As your referenced paper concluded, "CLL pathogenesis is characterized by a progressive loss of adaptive immune functions, including in most treatment-naïve patients, with preexisting memory being preserved longer than the capacity to mount responses to new antigens. In addition, higher NAb titers and response rates identify mRNA-1273 as a superior vaccine for CLL patients." I particularly liked the illustration of how our adaptive immunity drops over time (see attached image), which is why it is so important to get up to date with our (non-live) vaccinations as soon as we are diagnosed. See our Pinned Post on recommended vaccinations: healthunlocked.com/cllsuppo...

Note the second point (my underlining) in the section, What do these findings mean?

- Dissection of SARS-CoV-2 vaccine-induced humoral and cellular responses revealed a progressive deterioration of adaptive immune functions, even in CLL patients who had never received therapy.

- The “seroconversion” of over a quarter of CLL vaccinees likely reflects the presence of non-protective common coronavirus Abs that cross-react with the SARS-CoV-2 spike protein.

- Higher Ab response rates and NAb titers indicate that mRNA-1273 may be more beneficial for CLL patients.

- CLL patients and other immunocompromised populations may benefit from alternative vaccine regimens, which should be evaluated in clinical trials.

Those "non-protective common coronavirus Abs" would be associated with memory B cells from previous coronavirus (primarily cold) infections, the importance of which I mentioned yesterday healthunlocked.com/cllsuppo... though per the conclusion "Most importantly, our finding of the S+NAb- serotype in roughly a quarter of CLL vaccinees indicates that “seroconversion” does not necessarily indicate the mounting of a protective antibody response.", so more study is needed.

That's also what the authors are saying with respect to their last point, which you asked about. We know that people with CLL don't respond as well as healthy individuals to vaccinations, but respond better to some vaccines (such as mRNA-1273 than others). Hence the need for more clinical trials. Of note, there is growing evidence that mixing our COVID-19 vaccinations provides a better response than staying with the same vaccine provider.

There is still a large amount of misinformation and disinformation circulating about vaccinations, in particular the mRNA vaccines, which is why this meta-analysis of 54 studies, which mentions mRNA-1273 in the conclusion is relevant:-

The effectiveness of COVID-19 vaccines in reducing the incidence, hospitalization, and mortality from COVID-19: A systematic review and meta-analysis

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

A systematic search was performed independently in Scopus, PubMed via Medline, ProQuest, and Google Scholar electronic databases as well as preprint servers using the keywords under study...A total of 54 studies were included in this meta-analysis.

Conclusion

The results of this meta-analysis indicated that vaccination against COVID-19 with BNT162b2 mRNA, mRNA-1273, and ChAdOx1, and also their combination, was associated with a favorable effectiveness against SARS-CoV2 incidence rate, hospitalization, and mortality rate in the first and second doses in different populations. We suggest that to prevent the severe form of the disease in the future, and, in particular, in the coming epidemic picks, vaccination could be the best strategy to prevent the severe form of the disease.

Neil

We are more likely to gain greater protection from vaccinations earlier in our CLL journey

[BWHR in reply to AussieNeil]

Thanks for your quick and thorough response! We are big vaccine supporters, just trying to find the best one. To that end, I’m still a little confused by the technical jargon. One of your quotes suggests that mRNA vaccines are “superior” for CLL patients, but the overall gist I got from that paper was that they may NOT be best for CLL patients, and therefore alternatives should be explored. Can you speak more to that seeming contradiction? Thanks again!

[AussieNeil Partner Administrator in reply to BWHR]

I've asked my Aussie co-admin CLLerinOz , who had this to say, confirming my understanding:-

"While it does make scant reference to formulations of vaccines for other conditions, it seems to be emphasising other things more, saying that CLL patients need things like higher dose vaccines, adjuvants, bivalents and/or more frequent vaccination to elicit more reliable responses.

"Recent studies have shown that CLL patients benefit from adjuvanted zoster vaccines, including individuals on chronic BTK inhibition, but that hepatitis B immunization elicited poor or no responses in both treatment-naive and BTK inhibitor treated patients [8]. The effectiveness of pneumococcal and influenza immunization is also low in treatment-naive CLL patients, but has been observed to improve with higher dosing, adjuvant-conjugation, and earlier administration following diagnosis [6,7,61]. These results suggest that CLL patients with a reduced ability to mount de novo responses may benefit from more rationally designed vaccine regimens. Indeed, about a quarter of CLL patients who failed to respond to 2 SARS-CoV-2 mRNA immunizations, subsequently seroconverted following a third immunization [62,63]. Thus, CLL patients should be considered candidates for alternative vaccination regimens. For example, the high-dose flu vaccine, which is tailored for the elderly [64], may also elicit stronger and broader responses in CLL patients with partially impaired adaptive immunity. Similarly, a COVID vaccine that includes more than 1 variant may improve de novo responses. Clinical trials that formally test these possibilities should be of high priority."

"The higher neutralizing response rates and titers in mRNA-1273 vaccinees are likely due, at least in part, to the vaccine dose,"

" in addition to vaccine dose and formulation, vaccines will likely need to be updated to target newly emerging escape variants "

"our finding of the S+NAb- serotype in roughly a quarter of CLL vaccinees indicates that “seroconversion” does not necessarily indicate the mounting of a protective antibody response. "

"Future studies should consider the utility of vaccination to gauge the extent of disease-induced immune dysfunction in CLL patients and to gain greater insight into the underlying mechanisms."

Neil

[Jujy in reply to AussieNeil]

Hi Neil -Can you also give your thoughts on vaccine choices for those in remission (my husband is just completing V&O and we are hoping for a "deep" remission). I am not clear where he would fall on charts like the one above with the label "CLL Disease Progression."

[AussieNeil Partner Administrator in reply to Jujy]

As I understand it, with V&O, you are unlikely to see any antibody response for at least 12 months after the last O infusion, unless you were exposed to the illness or had the vaccine prior to developing. In the latter cases, you might have some memory B cells that could respond to boosters.

Other targeted therapy treatments and eventually V&O, might see an approved ability to respond to vaccinations after healthy B cell recovery, particularly if you've only had a short watch and wait.

Neil

[Jujy in reply to AussieNeil]

Thank you. It sounds like I should be encouraged that he had Covid in early 2022 (during the spike). In fact what we thought was long Covid was likely CLL. He was also up to date on boosters prior to treatment.

[Katie-LMHC-Artist in reply to AussieNeil]

Thanks for breaking this down for us. I did read that CLL patients benefit from adjuvanted zoster vaccines. I had the vaccine a few weeks ago and wanted to know how effective it was. Also, that CLL patients need a higher dose of pneumococcal and influenza vaccines.

[SofiaDeo in reply to Katie-LMHC-Artist]

This is true, but if I happened to be someone who generally gets strong reactions/side effects of vaccines, I am not sure I would want an adjuvanted one!

[Katie-LMHC-Artist in reply to SofiaDeo]

I get it! We all react differently to vaccines!

[BWHR]

Thanks again for the responses. The line that confused me is the one that says CLL patients have “lower binding antibody (Ab) and neutralizing antibody (NAb) titers than healthy individuals following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA vaccination.” I had read that to mean that the vaccine resulted in bloodwork that was worse than healthy individuals - meaning that the vaccine did something bad to the CLL patients’ numbers. I understand now that it means post-vaccination bloodwork showed a lower response to the vaccine than that seen in healthy individuals. Thanks to everyone for helping clear this up!

[81ue in reply to BWHR]

My understanding was lower response to vaccine was expected which is why boosters were important