We now have Covid19 vaccines. But will they work? As so many people are asking “should blood cancer patients take the COVID19 vaccine?” there is no direct data to answer how well theses vaccines will work in us. But most people will agree that it is worth taking them anyway since a chance of some immunity is better than none.

This post may be upsetting to some readers so proceed with caution if you are easily worried.

A recent study did try and address the broader question of how well do vaccines work in blood cancer patients, or rather CLL patients in particular. Whilst this data is specific to CLL, it is worth remembering that CLL is both a leukemia and a lymphoma so this data may at least have some implications for other blood cancers.

On that note it is perhaps worth saying that the general effect on the immune system of CLL is believed to be greater than some other types of blood cancer at least when those cancers are in watch and wait or remission. This is because the cancerous B lymphocytes of CLL even from early in the disease are affecting the whole body and interfere with healthy B lymphocytes.

Having said that the immune damage of CLL is progressive and so the more recently someone was diagnosed then generally the better their immune response. So in my own case, I was vaccinated with the pneumonia vaccine early on and I did get an antibody response to that. Since then as my general antibody level has dropped, the number of anti-pneumonia antibodies has also dropped. But on the last test I did still have a few pneumonia antibodies left.

On the other hand three and a half years into my cancer diagnosis, and eighteen months after finishing chemotherapy, a recent test vaccination for a different disease showed absolutely no antibody response in me. Why would that be?

In the earlier stages of CLL then it is sometimes the case that you already have only a few healthy B lymphocytes. If you do have enough lymphocytes a vaccination or indeed an infection with a new virus or bacteria will lead to the selection of lymphocytes that can make antibodies to that antigen. Those lymphocytes rapidly multiply, and some of them become plasma memory cells which continue to produce antibodies for years and can be triggered to multiply once more by another booster vaccine or infection with the same virus or bacteria. For more information see “How does the immune system work?”

Plasma memory cells are not destroyed by most chemotherapy regimes. But B lymphocytes can be entirely wiped out, especially by treatments which include rituxumab or other treatments which target b lymphocytes including venetoclax and CAR-T cells. When that treatment is stopped some people will grow back healthy b lymphocytes relatively quickly. But some people never do.

In the period after treatment there is really a bit of a double edged sword. If you see your lymphocyte count really low (below 1 or 1000 using US units) then you might be happy that your blood cancer is unlikely to be growing back (especially if it was CLL). But if your lymphocytes do start to climb do you rejoice that perhaps healthy ones are growing back or fear that your unhealthy ones are returning?

The reason that many people with CLL in particular see a gradual reduction in their antibody levels as measured by the immunoglobulin G levels (IgG) is that over time the plasma memory cells are going to gradually die out, and if you do not have enough healthy b lymphocytes they will not be replaced.

When someone has CAR-T or a stem cell transplant then the plasma memory cells are wiped out altogether which is why the advice is to have all your immunisations again. Giving immunisations is usually delayed, however, until b lymphocytes are bringing to grow back. In the case of a stem cell transplant that can sometimes be realtively quick (check with your team). In the case of a CAR-T cell treatment until the transfused CAR-T cells begin to die off they will be very good at killing off any lymphocytes healthy or cancerous.

In the case of the BTK inhibitors such as ibrutinib and acalabruinib they do not kill off the b lymphocytes aggressively but they do slow their growth and so it is hypothesised that they may reduce the effectiveness of vaccinations or indeed being presented with a virus or bacteria you have not seen before. They are not expected to have an effect on the plasma memory cells but of course if they are preventing those cells from being replaced you may also still see a decline in the immunoglobulin levels. The effects of these drugs are not uniform, however, and some people report an improvement in their immune response on them.

The study I would like to share the results of today looked at two groups of CLL patients. Those who were treatment naive, on watch and wait and those who were on a stable dose of ibrutninb or acalabrutinib. The treated group to be honest may well represent a better response than those who have been treated with other treatments for blood cancer, especially if their lymphocyte count is still low. The untreated group may on the other hand may be a worse response than some other untreated blood cancers.

In this study two vaccines were given. The first was a hepatitis B vaccine and it was only given to those who did not have prior evidence of immunity or infection with hepatitis B. This would therefore be testing the function of the B lymphocutes only. The second was the Shingrex vaccine which is a new shingles vaccine that is not live and so is potentially suitable for use in people with impaired immunity. Since almost everyone has had chicken pox as a child and so is likely to have some memory cells active against this virus then this vaccine is effectively a booster vaccine and will also potentially trigger the plasma memory cells. This may explain the results seen.

Original article reporting the effects of two vaccines in CLL patients

Although this study had relatively small numbers, it is possible to make an estimate of the percentage of CLL patients who will respond to each vaccine. We can also surround that estimate with confidence intervals. These give us the range in which we believe there is a 95% chance the true value will be.

Hepatitis B vaccine (presenting a new disease antigen)

• 28% of treatment naive patients who are in watch and wait did respond to this vaccine. (95% confidence intervals ranged from 15% to 45%).
• 4% of patients on acalabrutinib or ibrutinib responded to the vaccine with a 95% Confidence Interval of 0.7% to 18.9%.
• This difference was statistically significantly worse than treatment naive with a p value of 0.017. This means the chance of this finding being by chance is 1.7%.
• Since this was a new disease to those being vaccinated this reflects the activity of B lymphocytes and we see a relatively low response to the vaccine even in untreated patients.

Shringrex Vaccine (presenting an antigen most patients will have previously seen)

• 59% of treatment naive patients responded to this vaccine (95% Confidence Interval 38.7% to 76.7%)
• 41.5% of patients on acalabrutinib or ibrutinib responded (95% Confidence interval 27.8% to 56.6%)
• This difference was not statistically significant with a p value of 0.2 which means there was a 20% chance the difference seen is by chance.
• A larger study might either conclude that there is really no difference between these groups or that there is a small difference that this small study was not able to detect.
• Since this vaccine would in most patients also test the plasma memory cells perhaps that explains the better response seen in both groups of patients compared to the hepatitis B vaccine.

Side effects

There was no concern raised about additional side effects compared to the general population. No treatment-related serious side effects occurred in these studie. However, it is worth noting that over ten percent of patients in at least one of the vaccines experienced each of the following mild side effects; Pain, Myalgia, Rash maculo-papular, Fatigue, Headache, Injection site reaction, Flu like symptoms, Chills, Nausea.

A higher proportion of patients experienced those mid side effects than responded in terms of antibodies. So we can’t assume that if we have side effects to a vaccine it means it definitely worked. Antibody blood levels taken after a vaccine are the best way for blood cancer patients to be reassured that the vaccine has worked. Failure to respond to a vaccine in this way is often called “failing a test vaccine” by doctors and is one of the indications to consider IVIG or SCIG treatment.
https://bloodcanceruncensored.com/does-convalescent-plasma-work-what-is-ivig/

Immunoglobulin levels

None of the patients vaccinated had a very low immunoglobulin level with the lowest level being 404 (or 4 in UK units)

Conclusions

• We should not think that each blood cancer patient will get a reduced response to vaccines. The truth is instead that some of us get a FULL response to vaccines, whilst others may get a small response and others will get none. Someone like me who is on the brink of needing IVIG is likely to be in the group who get zero response (as indeed I got no response to a recent test vaccine)
• In the study low numbers of CLL patients responded to any of these vaccines but some did.
• Response rates to other vaccines may vary
• Response rates will likely be better the sooner after diagnosis someone is vaccinated
• Other blood cancer treatments many lead to an even lower vaccine response rate, specially if the lymphocyte count is low.
• Most experts will still advise most blood cancer patients should still take vaccinations including COVID19 vaccines. For specific advice about your own medical situation please discuss with your specialist doctor.
• Some doctors suggest a short pause in ibrutinib or acalabrutinib before vaccination might lead to better results. Do not do this without first discussing with your CLL expert.
• Antibody testing after any vaccine is the only way to know if that vaccine has worked for you. In the case of COVID19 vaccines ensure you test for spike protein antibodies not any other part of the virus.
• Some patients who are concerned they may not respond to the COVID19 vaccine may wish to consider volunteering for a monoclonal antibody trial

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More articles on COVID19 are also available