Pausing BTKi for Vaccine Did Not Boost Immunity in CLL

Pausing treatment during vaccination did not improve immunity in patients with chronic lymphocytic leukemia and should not be recommended: © stock.adobe.com.

Pausing Bruton's tyrosine kinase inhibitors (BTKi) therapy around the time of vaccination was not beneficial for immunity and should not be recommended in clinical practice for patients with chronic lymphocytic leukemia currently undergoing such therapy, according to study findings published in The Lancet.

“This randomised trial found no benefit in pausing BTKi therapy around the time of vaccination with a SARS-CoV-2 booster,” wrote lead study author Dr. Jonathan A Cook and colleagues. “As such, in clinical practice, individuals should not be recommended to pause their BTKi therapy to enhance immunity to vaccination.

Cook works in the Oxford Clinical Trials Research Unit at University of Oxford, Oxford, UK.

Between Oct. 10, 2022, and June 8, 2023, 99 individuals (72% male, 28% female; 90% White) were randomly assigned to pause (51%) or continue (49%) their BTKi therapy and were observed for 12 weeks. Three weeks after vaccination, the geometric mean anti-spike-RBD-specific antibody level was 218.8 U/mL (SD 122.9) in those who continued treatment and 153.4 U/mL (SD 103.2) in those who paused. This indicates that, on average, patients who continued their BTKi therapy had higher antibody levels three weeks after vaccination compared with those who paused treatment.

The geometric mean ratio was 1.104, which means that the antibody level in those who continued was about 10.4% higher than in the those who paused. One serious side effect occurred: a participant in the pause group died from COVID-19 infection two months after randomization.

A serious side effect which occurred during the 12-week follow-up was the death of one participant in the pause group from COVID-19 infection two months after randomization.

“The results highlight the importance of testing treatment interventions in a powered, randomised setting but also the need for more fundamental science to consider the drivers of the heterogeneous responses observed,” wrote Cook. “This vulnerable group continues to be at risk from infections and necessary precautions should be adopted where available, such as monoclonal antibody prophylaxis.

Chronic lymphocytic leukemia is the most common type of leukemia and is linked to significant immunosuppression. Although BTKis have transformed treatment, according to the study, they impair vaccine-induced immunity.

Furthermore, the data showed that both study groups had strong cellular immune responses that improved after vaccination, suggesting the immune system can recognize and respond to newer variants despite changes in the virus.

Pausing treatment did not affect quality of life, and most patients followed their doctor’s advice, with only two patients restarting early. Some individuals reported temporary lymph node swelling, which resolved without medical help by 12 weeks. Vaccination remains important, especially before starting continuous therapy, though how these findings apply to other vaccines like shingles is unclear, according to study authors.

Additionally, most patients received an mRNA vaccine targeting the original COVID-19 strain, though a few received a protein-based version. Since fewer patients enrolled than expected and vaccine types varied, differences in antibody responses cannot be ruled out, as per the study.

Methods of the Trial

This study included adults with chronic lymphocytic leukemia on BTKi therapy for at least 12 months. Patients either paused treatment for 3 weeks around their COVID-19 booster or continued as usual. Most received a bivalent mRNA vaccine. The main goal was to measure antibody levels 3 weeks after vaccination.

The primary outcome was the anti-spike RBD-specific antibody titer three weeks after vaccination, analyzed by intention to treat after trial completion.

Reference

“A 3-week pause versus continued Bruton tyrosine kinase inhibitor use during COVID-19 vaccination in individuals with chronic lymphocytic leukemia (IMPROVE trial): a randomised, open-label, superiority trial,” by Dr. Jonathan A Cook, et al., The Lancet.

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