Interruption of BTK inhibitor improves response to SARS-CoV-2 booster vaccination in patients with CLL

Abstract

B-cell targeted therapies, including anti-CD20 monoclonal antibodies (mAb) and Bruton’s tyrosine kinase inhibitors (BTKi), further suppress antibody (Ab) response to vaccines in patients with chronic lymphocytic leukemia (CLL). We conducted a prospective cohort study of SARS-CoV-2 vaccination in 81 CLL patients receiving BTKi (n = 54), venetoclax (VEN, n = 9), or who were treatment naïve (TN, n = 18). Anti-spike Ab were detected in 53% of patients on BTKi post-primary series and 84% post-booster, 57% of patients on VEN post-primary series and 50% post-booster, and 67% of TN patients post-primary series and 87% post-booster. T-cell response to the primary series was independent of Ab response. At the time of booster, 12 patients interrupted BTKi (median 21 d, range 8–22) and 33 continued BTKi. Among patients with detectable Ab post-booster, those who interrupted BTKi (n = 10) had significantly higher Ab titers (median 7149 units/mL) compared with patients who continued BTKi (n = 27, median 2071 units/mL, p = .04).

Keywords:

• Vaccines
• neoplasia
• lymphoid leukemia
• neoplasia
• the humoral immune response
• immunobiology
• T-cell mediated immunity
• immunobiology

Author contributions

• Emily Tomasulo was the primary author and conducted data analysis and figure formation.

• Shira Paul assisted with manuscript authorship.

• Jonathan Chen assisted with data extraction.

• Rui Mu performed T-cell analysis.

• Xin Tian assisted with data analysis and figure formation.

• Christopher Pleyer and Adrian Wiestner contributed to study design and manuscript authorship.

• Clare Sun contributed to data extraction, data analysis, study design, figure formation, and manuscript authorship.

Disclosure statement

Adrian Wiestner received research support from Pharmacyclics LLC, an AbbVie Company, Acerta Pharma, a member of the Astra-Zeneca group, Merck, Nurix, Verastem, and Genmab. Clare Sun received research funding from Genmab.

Additional information

Funding

This research was supported in part by the Intramural Research Program of the NIH and NHLBI.