IMPROVE: Continued BTKi use vs a 3-week pause before COVID-19 vaccination in CLL

While BTKis have revolutionized CLL management, they are associated with impaired vaccine-induced immunity. Observational data indicate that immunity may be improved by a short pause in BTKi treatment around the time of vaccination. However, this approach has not been evaluated in prospective studies, leading to conflicting recommendations regarding the use of BTKis.

Cook et al. conducted a two-arm, parallel-group, superiority, randomized controlled trial (IMPROVE, ISRCTN 14197181), which enrolled patients with CLL across 11 UK hematology clinics to evaluate the impact on antibody responses of continuous BTKi use vs a 3-week BTKi pause. Findings were published in The Lancet Hematology.¹

Eligible patients (N = 99) with a diagnosis of CLL who had been on either ibrutinib or acalabrutinib for at least 12 months were randomized 1:1 to receive continuous BTKi (n = 49) or to have a 3-week pause (n = 50). The primary outcome measure was RBD antibody titers 3 weeks after SARS-CoV-2 booster vaccination. Key secondary outcomes included RBD titers at 12 weeks and safety.

Key learnings

At 3 weeks, the geometric mean RBD antibody titer was 218.8 U/mL in the continue group vs 153.4 U/mL in the pause group (GMR 1.104; 95% CI, 0.565–2.158; p = 0.770). 

No difference in RBD antibody titer was observed between the continue group (177.6 U/mL) and the pause group (122.4 U/mL) at 12 weeks (GMR 1.037; 95% CI, 0.529–2.035; p = 0.91).

At 12 weeks, one participant reported lymphadenopathy in the pause group vs no reports of lymphadenopathy in the continue group. While there were no hospital admissions reported, one participant in the pause group died due to COVID-19 infection.

This trial found no benefit from pausing BTKi therapy during SARS-CoV-2 booster vaccination in patients with CLL and suggests that a pause should not be recommended to enhance immunity during vaccination in clinical practice.