New research provides definitive guidance for blood cancer patients undergoing COVID-19 vaccination while on targeted therapy. A randomized clinical trial has determined that patients with chronic lymphocytic leukemia (CLL) taking Bruton Tyrosine Kinase inhibitors (BTKi) should maintain their cancer treatment during COVID-19 vaccination, contradicting earlier observational data.
The findings, published in The Lancet Haematology, come from the IMPROVE trial led by researchers at the University of Birmingham and the Oxford Clinical Trials Research Unit. This study represents the first randomized controlled investigation into whether temporarily pausing BTKi therapy improves vaccine response in this vulnerable patient population.
No Advantage to Pausing Cancer Treatment
The trial enrolled 99 adults with well-controlled CLL from 11 UK hospitals who had been on BTKi therapy—such as ibrutinib or acalabrutinib—for over a year. Participants were randomly assigned to either pause their medication for three weeks (one week before and two weeks after vaccination) or continue treatment without interruption.
Researchers measured anti-spike-RBD-specific antibody titers at baseline, three weeks post-vaccination, and at the 12-week mark. The results showed no statistical difference between the groups, with geometric mean antibody titers of 218.8 U/mL in the continuous therapy group versus 153.4 U/mL in the paused therapy group at three weeks.
"Our study provides clarity for blood cancer patients and their healthcare providers, that pausing BTKi therapy around the time of COVID-19 vaccination does not improve their antibody response and should not be recommended in clinical practice," said Dr. Helen Parry, Associate Professor at the University of Birmingham's Department of Immunology and Immunotherapy and Chief Investigator of the IMPROVE trial.
Understanding CLL and COVID-19 Vulnerability
CLL is the most common adult leukemia and is characterized by an overproduction of abnormal B lymphocytes. Patients with this condition are particularly vulnerable to infections due to their compromised immune systems, making effective vaccination strategies crucial.
The COVID-19 pandemic posed significant challenges for CLL patients, who experienced higher mortality rates from SARS-CoV-2 infection compared to the general population. Additionally, these patients typically mount weaker responses to vaccines, with previous studies showing response rates as low as 15.3% to COVID-19 vaccination among those on BTKi therapy.
BTK inhibitors work by blocking a protein that helps cancer cells survive and multiply. While effective at controlling CLL, these medications can further suppress immune function, potentially limiting vaccine efficacy.
Clinical Implications and Safety Considerations
The study revealed an unexpected finding: patients receiving first-line BTKi therapy actually had lower antibody titers compared to those on later lines of treatment. This suggests that the relationship between BTKi therapy and immune response is complex and warrants further investigation.
While pausing therapy did not improve vaccine response, researchers noted that participants who temporarily stopped their medication reported higher rates of lymphadenopathy (swollen lymph nodes), though other disease flare symptoms were similar between groups.
The trial recorded one serious adverse event—a patient in the pause group died from COVID-19 infection approximately two months after entering the study.
Heterogeneous Responses and Future Research
A key observation from the study was the highly variable antibody responses among patients, regardless of whether they paused or continued treatment. This heterogeneity highlights the complexity of immune responses in CLL patients and suggests that personalized approaches may be necessary.
"We observed a plateau effect in some patients who had already received multiple vaccine doses," explained the researchers. Most participants had received at least four prior COVID-19 vaccinations before entering the trial.
The research team acknowledged that their study was slightly underpowered due to its size, meaning a small benefit to pausing therapy cannot be completely ruled out. However, the current evidence does not support recommending treatment interruption.
Additional research using blood samples collected during the trial is now underway, funded by UK Research and Innovation and Blood Cancer UK. This work aims to better understand the immune response to COVID-19 vaccination in CLL patients and identify potential strategies to enhance protection in this vulnerable population.
Practical Guidance for Patients and Clinicians
For the estimated 20,000 people living with CLL in the UK and thousands more worldwide, these findings provide clear guidance: continue BTKi therapy during COVID-19 vaccination. This eliminates unnecessary treatment interruptions while ensuring patients maintain protection against their underlying cancer.
Healthcare providers can now confidently advise patients to maintain their regular medication schedule when receiving COVID-19 vaccines, simplifying clinical management and potentially reducing anxiety among patients concerned about optimal vaccination strategies.
The study also reinforces the importance of additional protective measures for CLL patients, including booster vaccinations, infection prevention practices, and prompt treatment of breakthrough infections.
