Tuesday 01 April 2025
Lay Summary
The IMPROVE study: Investigating if pausing a Bruton Tyrosine Kinase inhibitor drug for three weeks improves the antibody response to COVID-19 vaccination
This document is a plain English summary of the main results of the study.
Summary: The results of the study show that pausing Bruton tyrosine kinase therapy for 3 weeks around the time of COVID-19 vaccination does not improve antibody responses.
Our thanks to everyone who took part in IMPROVE, the members of our Patient Advisory Group, and staff who helped run the study at each hospital
Why was the research needed?
Vaccination helps the white blood cells (lymphocytes) produce antibodies (a type of protein). This is called the antibody response to vaccination. These antibodies may then help the body fight infection.
Following COVID-19 vaccination people with CLL have lower antibody levels than people in the general population. For those taking a Bruton Tyrosine Kinase inhibitor (BTKi) drug, such as ibrutinib or acalabrutinib, antibody levels after vaccination are often even lower. Previous information suggested that pausing the BTKi drug around the time of vaccination may improve the antibody response.
What were the main questions studied?
For people with CLL the trial studied whether a short pause in taking their BTKi drug, for one week before and two weeks after, their COVID-19 vaccination improved their antibody response. We measured the immune response of people who took part in the study before vaccination and again three weeks afterwards.
We also measured the immune response 12 weeks after vaccination, and asked whether people who took part in the study had any side effects.
Who took part?
Participants joined the study between October 2022 and June 2023. 99 adults who had been taking a BTKi drug for more than one year and whose CLL was well controlled took part at 11 hospitals in the UK.
People who took part in the study were similar in age, biological sex and ethnicity to those with CLL in the UK. For two thirds of participants the BTKi drug was their first treatment for CLL. For half acalabrutinib was their BTKi drug and for the other half it was ibrutinib. Most participants had had five previous COVID-19 vaccinations before taking part in IMPROVE.
What happened during the study?
As this was a randomised trial, for each person the decision about whether to pause their BTKi drug was decided by chance, rather like tossing a coin. This process is called randomisation. A computer chose which treatment each participant received. Neither they nor their doctor were able to choose.
What treatments did the participants receive?
49 participants paused their BTKi drug for three weeks. They were asked to stop the drug one week before their vaccination date and restart it two weeks after vaccination. 50 participants continued taking their BTKi drug as usual.
What side effects did the participants have?
No participants reported serious side effects. Three participants withdrew from the study, two from the pause BTKi drug group and one from the continue BTKi drug group. One participant died during the study from infection.
In the pause group, four participants said they had swollen glands (lymph nodes) three weeks after vaccination; at 12 weeks only one participant reported swollen glands. No swollen glands were reported by those in the continue group. Having a high temperature was reported by one participant at three weeks in the pause group, and by no participants in the continue group. The levels of white blood cells also remained similar in the two groups.
What did the results show?
Participants in the group who paused their BTKi drug had a similar level of COVID-19 antibodies three weeks after vaccination to those in the group who continued their BTKi drug. The quality of the antibody response was also similar in both groups. The immune response remained similar between the two groups 12 weeks after vaccination.
The number of participants who had no COVID-19 antibody response when they joined the study but did have a response after vaccination was also similar in both groups.
How are these results helping people with CLL?
We found no clear evidence that a short pause in their BTKI drug improves the immune response to COVID-19 vaccination for people with CLL. Therefore, people with CLL should continue their BTKi drug as normal when getting their COVID-19 vaccination.
Future research using blood samples from the study will aim to understand more about how people with CLL respond to COVID-19 vaccination, and how this response might be improved.
Trial registration number: ISRCTN 14197181
Thursday, 28 September 2023
The IMPROVE study protocol has been published in the open-access journal BMJ Open. You can read it here.
Friday, 30 June 2023
The IMPROVE study is now closed to recruitment, with 99 participants consented and randomized.
Friday, 30 September 2022
The IMPROVE study opened to recruitment!
