Q&A - COVID-19 vaccines and Chronic Lymphocytic Leukaemia (CLL)

New research from a team of researchers at the University of Birmingham has shown that 20% of people with Chronic Lymphocytic Leukaemia produce no antibodies to fight the virus after four vaccine doses.

The results also suggested that the proportion of people who develop an antibody response levels out after the third dose (a fourth dose didn’t appear to improve the rate further).

The following factors were found to be independently associated with a weak antibody response to vaccination:

  • low levels of immunoglobulin
  • ongoing treatment with Bruton tyrosine kinase inhibitors, a drug used to treat leukaemia
  • treatment immediately after vaccination

Levels of T cells in the study participants after three or four vaccine doses were found to be comparable to those seen in the control group after two doses of vaccine, and were substantially higher in those who had received the AstraZeneca vaccine as their primary course. These T cells were equally good at recognising the Omicron variant as those seen in people without CLL.



Do you think the results of this study would be similar for other types of leukaemia / blood cancer?

We know that overall, people with blood cancer have poorer responses to the COVID-19 vaccines, but studies are emerging which show that responses do vary depending on the type of blood cancer and the type of treatment people are receiving.

There may also be differences in responses seen in the two different ‘arms’ of the immune system (the humoral side which makes antibodies and the cellular side which includes T cells) depending on the type of blood cancer someone has. We are still learning and hope further research will help to clarify these differences.

People who previously had COVID-19 were excluded from the study – would you expect their responses to vaccination to be more robust? Have any studies looked at immune responses in people with prior infection?

In a previous paper we published as part of this study, we showed that some people with CLL who get COVID-19 mount robust antibody responses, but unfortunately this is not true in every case. From the small number of infections we have seen in our study cohort, those who didn’t generate antibodies after vaccination sometimes still had none even after recovering from COVID-19.

People on Bruton tyrosine kinase inhibitors and those with low immunoglobulin levels were more likely to have no antibodies, even after being infected.

How would someone find out if they are one of the people who generated a good antibody response, or one of the 20% that didn’t?

This is a question on a lot of people's minds, for obvious reasons. At the moment, we are still understanding all the factors that underpin an effective immune response, including the respective roles of antibodies, T cells and other contributors too. This is a very complex picture (our data actually showed a slight increased risk of infection among those with antibodies, likely due to factors like age and social behaviours).

At the moment, the best advice would be to continue taking the usual measures to reduce infection risk. With further research, we hope that it will become possible to more accurately determine an individual's immune response and risk.

Would ‘treatment holidays’ be viable for people with CLL (as have been tested in people with other conditions) to give them a chance to mount an immune response?

This is a really good question and one we and others are keen to find answers to.

The IMPROVE study (funded by NIHR) is a clinical trial aiming to study this, and is due to get under way before the planned COVID-19 boosters in autumn 2023. Participants with CLL who take a Bruton Tyrosine Kinase inhibitor will be enrolled and randomised to either pause their therapy for three weeks around the time of vaccination, or continue as normal with their treatment.

T cell responses were generally shown to be good in this study – would a good T cell response alone give someone adequate protection?

The cellular immune responses show good protection against the Omicron variant. They may not be so useful at protecting against getting infected (although this is currently still being researched) but the T cells produced by the vaccine will be able to recognise cells once they have become infected with the virus and help to destroy the virus and aid recovery.

The researchers noted that adenoviral-based vaccines like AstraZeneca seem to promote a better T cell response. What advice would you give someone who has only received mRNA vaccine doses?

This is a small study and larger studies looking at protection from boosters in healthy people have shown responses to be similar in people who had either AstraZeneca or a mRNA vaccine (Pfizer or Moderna) as their primary course. It’s likely that subsequent doses of mRNA booster vaccine will achieve similar results. The mRNA vaccines have been shown to generate better antibody responses and this is the main reason they are now recommended.

What are the various ‘alternative approaches for immune protection’ that might be available to people who don’t mount an immune response? Which are available now?

Monoclonal antibody therapy and anti-virals are available in the UK to those who are immunocompromised and test positive for COVID-19. They are very effective and reduce the risk of admission to hospital by up to 90%. These therapies became available during the appearance of Omicron and emerging data shows reduced hospitalisation rates during the same time period, which is encouraging. We would encourage eligible people to access these therapies through a COVID Medicines Delivery Unit if they test positive.

Evusheld is a monoclonal antibody intended for preventative use. Although it is licensed in UK, it is not yet available.

Should people with CLL still be shielding?

Even before the pandemic, people with CLL were at increased risk of respiratory infections and are used to being cautious. We would advise people to consider the risks of social interactions and try to mitigate against this by taking precautions such as meeting outdoors where possible. COVID-19 is most likely here to stay.

Raising awareness of the importance of accessing therapies as soon as eligible people test positive for COVID-19 is also really important.

Will people with CLL need subsequent (or regular) doses of COVID-19 vaccine to remain protected?

Yes, evidence suggests that subsequent boosters are likely to further improve levels of immunity. The Government has already indicated that it anticipates an autumn booster programme for vulnerable people including those with CLL.