How effective is COVID-19 vaccination in people with lymphoma?

We know a lot of people have questions about whether coronavirus vaccination works for people who have lymphoma. Here, we summarise what we know – and what we don’t know – so far.

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What we know

Early results of trials testing the vaccines in people with lymphoma

Ongoing and future research

Guidance for people with lymphoma

Person using a needle and syringe to draw vaccine from a bottle

We know that people affected by lymphoma are at higher risk than other people of becoming seriously ill if they develop COVID-19. This is why they were prioritised for vaccination when it first became available in the UK. However, we also know that people with lymphoma often have lowered immunity and might not respond as well to vaccines as other people.

Although the coronavirus vaccines have all been tested in very large clinical trials involving tens of thousands of people, the trials didn’t include people with lymphoma. This means, at the moment, there is limited information on how well the vaccines work in people with lymphoma.

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Early results of trials testing the vaccines in people with lymphoma

Some general trials have included a small number of people with lymphoma and other types of blood cancer. Other trials are looking specifically at how effective coronavirus vaccination is for people with lymphoma and other types of cancer. Some of these have published early results. We summarise some of the important trials here.

SOAP trial

Early results from a trial looking at vaccine responses in people with cancer (the SOAP trial) suggested that people with lymphoma have a lower antibody response to coronavirus vaccination than the public at large. This trial included 34 people with lymphoma or CLL. Early results suggested that many people with lymphoma might not make sufficient protective antibodies in response to the coronavirus vaccine, but the small number of people with lymphoma who took part makes it difficult to draw any firm conclusions.

Most of these people had only had one dose of vaccine, and we don’t know how a second dose affects the antibody response in people with lymphoma. It’s also important to remember that your immune system is very complicated. Antibodies aren’t the only way your body responds to vaccination (although they are the easiest response to measure). We don’t know yet how other parts of your immune system respond to the vaccines, or how antibody levels relate to your overall protection from COVID-19.

Virus Watch study

The Virus Watch study, run by University College London and the NHS, has measured antibody responses in people who had their vaccine as part of the UK vaccination programme, rather than part of a clinical trial. This study included over 8,500 people. Of these, 74 reported that they had blood cancer. The data released so far does not specify what types of blood cancer, so we don’t know how many of these people had lymphoma. Early results found that 70% of people with blood cancer produced antibodies within 28 days of having their first vaccination. Although this is lower than in people without blood cancer, the result is more encouraging than some other studies report. After a second dose of vaccine, the proportion of people with blood cancer who had an antibody response increased to 80%. People with blood cancer had significantly lower antibody levels than people without blood cancer, but we don’t know what this means in terms of the level of protection against COVID-19. Low antibody levels may still offer useful protection, while normal antibody levels do not guarantee complete protection against COVID-19. It is important to note that the number of people with blood cancer in this trial was small. The results haven’t yet been published or reviewed by other scientists.

Birmingham CLL/SLL trial

A study conducted in Birmingham has looked at responses to two doses of either the Pfizer/BioNTech vaccine or the Oxford/AstraZeneca vaccine in 299 people with CLL or SLL. In this study, most people had their second dose 10 to 12 weeks after the first. Around 1 in 3 people with CLL or SLL produced antibodies after their first dose of vaccine. After the second dose, this increased to around 3 in 4 people. Antibody levels were lower than in people without CLL or SLL, but scientists aren’t sure how this relates to the level of protection against COVID-19. People on active monitoring (watch and wait) were more likely to respond to vaccination than people on current treatment, especially people taking BTK inhibitors (for example, ibrutinib).

The PROSECO trial

The PROSECO trial is looking specifically at how well people with lymphoma respond to COVID-19 vaccination, and how long the immune response to the vaccine lasts. It is recruiting 680 people affected by lymphoma.

Early results were published after the first 129 participants had received two doses of either the Pfizer/BioNTech or Oxford/AstraZeneca vaccine. They showed that:

  • Most people with Hodgkin lymphoma or high-grade (fast-growing) non-Hodgkin lymphoma who had finished lymphoma treatment more than 6 months before being vaccinated had a strong antibody response to vaccination. An exception to this was people who had had CAR T-cell therapy, who did not produce antibodies after having the vaccine. However, the number of people who had had CAR T-cell therapy was very small, which makes it difficult to draw firm conclusions from the results.
  • Most people with low-grade (slow-growing) non-Hodgkin lymphoma who were not on treatment produced antibodies in response to two doses of vaccination but their antibody levels were lower than those of people with high-grade or Hodgkin lymphoma who were not on treatment. At the moment, researchers don’t know how antibody levels relate to your overall protection from COVID-19. Low antibody levels might still offer useful protection, while normal antibody levels do not guarantee complete protection.
  • People who had had treatment for lymphoma within the past 6 months were much less likely to respond to vaccination than those who had not had treatment in the past 6 months. Around 3 in 5 people who had had treatment in the past 6 months did not produce antibodies in response to vaccination.
 
It is reassuring to see that most people with Hodgkin lymphoma or diffuse large B-cell lymphoma who finished treatment more than 6 months ago were able to develop antibodies after vaccination. More research is needed into the immune response to vaccination for people with other types of lymphoma.
Professor Tim Illidge, Professor Of Targeted Therapy and Oncology, The Christie Hospital, Manchester

It is important to note that these are early results and, at the moment, the number of people in the trial with each different type of lymphoma is small. This makes it difficult to interpret the data. The trial has only measured antibody responses to vaccination and has not assessed other parts of the immune response.

Lithuanian trial

A clinical trial in Lithuania analysed antibody responses to the Pfizer/BioNTech COVID-19 vaccine in 885 people with blood cancers, including 286 with lymphoma or CLL.

Overall, people with blood cancers had much lower antibody responses than people without blood cancers. In particular, people who were on active treatment with BTK inhibitors (such as ibrutinib or acalabrutinib), venetoclax, or antibody therapies targeting a protein called CD20 (such as rituximab or obinutuzumab) had very low antibody responses. People who had received a stem cell transplant more than 6 months before vaccination generally had good antibody responses.

At the moment, scientists don’t know how antibody levels relate to your overall protection from COVID-19. The trial did not look at other parts of the immune response to vaccination, such as T-cell responses.

Public Health England data on vaccine efficacy in at-risk groups

You may have seen media coverage on Public Health England’s report on COVID-19 vaccine efficacy in clinical risk groups. This reported high response rates after two doses of vaccine in people who were immunosuppressed. However, the analysis grouped all immunosuppressed people together and did not compare response rates in people with immunosuppression caused by different conditions. We do not know if any of the people in the immunosuppressed group had blood cancer, so we do not know how this information relates to people with blood cancer.

Public Health England have since clarified their position:

 
Within these clinical risk groups, there will be people with more severe forms of illness – particularly in the immunosuppressed group – who may not respond as well to the vaccines, and we recommend they seek advice from their specialists.
Public Health England

While research into vaccine efficacy in people with lymphoma continues, it is important to follow any specific advice your medical team gives you and continue to take precautions to reduce your risk of infection.

Trial in people with B-cell blood cancers

An ongoing trial is measuring vaccine responses in people with B-cell blood cancers, including low-grade and high-grade non-Hodgkin lymphomas, chronic lymphocytic leukaemia (CLL) and Waldenström’s macroglobulinaemia.

The trial has reported preliminary results from the first 55 people involved in the trial.

  • 25 people were currently on treatment.
  • 18 people had finished treatment within the last 6 months.
  • 12 people had finished treatment more than 6 months ago.

Overall, the trial found that 20 people (36%) developed antibodies after their first dose of vaccine, rising to 23 (42%) after the second dose. People who had finished treatment more than 6 months ago were much more likely to develop antibodies than those on treatment or who had recently finished treatment.

In people who produced antibodies, the trial also measured how effective these antibodies were at neutralising the virus. Only 21 people were involved in this part of the trial. In total, 14 produced effective antibodies, including all of the people who had finished treatment more than 6 months ago.

This trial did not measure T-cell responses to vaccination.

Leukemia and Lymphoma Society study

A study from the Leukemia and Lymphoma Society in the US measured antibody responses after two doses of COVID vaccination with either the Pfizer or Moderna vaccine in 1,495 people with a variety of blood cancers.

The results found that people with Hodgkin lymphoma or high-grade non-Hodgkin lymphomas were more likely to respond to vaccination than people with low-grade non-Hodgkin lymphomas.


Percentage of people with different types of lymphoma who produced antibodies after two doses of vaccination

  • Hodgkin lymphoma 98%
  • Non-Hodgkin lymphoma
    • T-cell non-Hodgkin lymphoma 85%
    • Diffuse large B-cell lymphoma 79%
    • Follicular lymphoma 78%
    • Waldenström’s macroglobulinaemia  74%
    • Marginal zone lymphoma 62%
    • Mantle cell lymphoma 44%
    • Non-Hodgkin lymphoma – type not specified 79%
  • Chronic lymphocytic leukaemia 64%

The study also analysed vaccine responses based on what treatment people had received within the last 2 years. This showed that people who had had treatment that targeted B cells within the last 2 years were less likely to respond to vaccination than people who had had other types of treatment. B cells make antibodies so this is not an unexpected finding. It’s important to note that these results were not analysed based on the type of blood cancer people had, so they include people with myeloma and leukaemia as well as lymphoma. Most types of lymphoma develop from B cells.


Percentage of people who had received treatment for blood cancer within the last 2 years who produced antibodies after two doses of vaccination

  • Treatments that do not specifically target B cells
    • Chemotherapy 74%
    • Stem cell transplant 89%
  • Treatments that specifically target B cells
    • Rituximab or obinutuzumab 37%
    • Ibrutinib, acalabrutinib, zanubrutinib or pirtobrutinib 47%
    • Venetoclax 39%
    • CAR T-cell therapy targeting the CD19 antibody 14% (only 7 people in the study had had this treatment)

The trial by the Leukemia and Lymphoma Society did not measure T-cell responses to vaccination so it doesn't tell us how other parts of the immune system might respond to vaccination. Because it was carried out in the US, everybody in this trial had the Pfizer or Moderna vaccines and it doesn't include anybody who had the AstraZeneca vaccine. We don't know how or if this might affect the response.

Study of Pfizer vaccine in people with B-cell non-Hodgkin lymphomas

A trial carried out at a hospital in Israel measured antibody responses to two doses of the Pfizer vaccine in 149 people with low-grade (slow-growing) or high-grade (fast-growing) B-cell non-Hodgkin lymphomas. The results were analysed based on whether or not people had received antibody therapy with rituximab or obinutuzumab. These treatments target B cells – the immune cells that make antibodies.

  • 89% of people with B-cell non-Hodgkin lymphoma who had never been treated with rituximab or obinutuzumab produced antibodies in response to vaccination.
  • 67% of people with B-cell non-Hodgkin lymphoma who had been treated with rituximab or obinutuzumab more than 6 months ago produced antibodies in response to vaccination.
  • 7% of people with B-cell non-Hodgkin lymphoma who were currently on rituximab or obinutuzumab treatment, or had had it in the last 6 months, produced antibodies in response to vaccination.

These results are similar to those of other trials, which suggest people who are on, or have recently had, treatments that lower their immune system are less likely to respond to vaccination. The trial did not measure T cell responses to vaccination.

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Ongoing and future research

Lymphoma Action is working with other blood cancer charities and with a broader group of charities to keep vaccine efficacy at the top of the agenda and put the concerns of all of our beneficiaries to the Joint Committee on Vaccination and Immunisation (JCVI).

Lots of clinical trials are already taking place to try to find out more about how well the vaccines work in people with lymphoma and other blood cancers. These include the PROSECO trial, which is looking specifically at how effective coronavirus vaccination is in people with lymphoma. We endeavour to support these trials by raising awareness of the trial sites (currently Leicester, Norwich, Nottingham, Newcastle, Oxford, Portsmouth and Southampton).

Another trial called OCTAVE DUO is looking into whether a booster dose is effective in immunosuppressed people who may not have responded well to their first two doses of COVID-19 vaccine. This trial includes people with lymphoma.

In time, more research will become available. Blood Cancer UK have set up a vaccine task force, which aims to identify and address potential gaps in Covid-19 vaccine research for patients with blood cancer, and also regularly post updates on the latest research on COVID-19 vaccines in people with blood cancers.

Other trials are looking into approaches to protect people who can’t have a vaccine. These include the PROVENT trial, which is looking at whether lab-made antibodies can help prevent COVID-19 in people who can’t have (or don’t respond to) vaccination. Early results suggest that it is effective at reducing the risk of developing symptomatic COVID-19. Treatments for COVID-19 are also becoming available, such as dexamethasone and Ronapreve.

It is encouraging that this research is taking place, but it will be a while before full results are available. We will report results as soon as we have access to them.

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Guidance for people with lymphoma

Even if you don’t respond fully to vaccination, all the health professionals we have spoken to have stressed that ‘Any or some protection is better than none.’ This is why we recommend the flu vaccination every year, even when people are receiving chemotherapy. However we know how anxious you might be about the risk of COVID-19, especially if you feel that you have little protection even with the vaccine.

In the meantime, irrespective of your health status or predicted antibody levels, it is important to follow the government guidance and continue to take extra precautions to reduce your risk of infection. We have more information in our guidance for clinically extremely vulnerable people in England and the devolved nations.

Clinically extremely vulnerable people will be a priority group to receive a booster vaccination from September onwards. Household members of clinically extremely vulnerable people will also be eligible for a booster, which helps protect those at higher risk. It is also reassuring to note that vaccine uptake across the UK has been very high. This also helps protect people who either can’t have, or don’t respond to, vaccination because vaccinated people are less likely to pass the virus on.

You might find some of our other resources helpful:

We appreciate that this might be a worrying time. If you’d like to talk, contact our Helpline Services on freephone 0808 808 5555 from 10am to 3pm, Monday to Friday, or via Live Chat through our website. You can also email us at information@lymphoma-action.org.uk.