Effect of Bruton tyrosine kinase inhibitor on efficacy of adjuvanted recombinant hepatitis B and zoster vaccines

• Published in: Blood 2021-01, Vol.137 (2), p.185-189
• Main Authors: Pleyer, Christopher, Ali, Mir A., Cohen, Jeffrey I., Tian, Xin, Soto, Susan, Ahn, Inhye E., Gaglione, Erika M., Nierman, Pia, Marti, Gerald E., Hesdorffer, Charles, Lotter, Jennifer, Superata, Jeanine, Wiestner, Adrian, Sun, Clare
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic; Agammaglobulinaemia Tyrosine Kinase - antagonists & inhibitors; Aged; Brief Report; Female; Hepatitis B Vaccines - immunology; Herpes Zoster Vaccine - immunology; Humans; Immunity; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Male; Middle Aged; Patient Outcome Assessment; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Vaccination; Vaccines, Synthetic - immunology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2020008758

Vaccinations are effective in preventing infections; however, it is unknown if patients with chronic lymphocytic leukemia (CLL) who are treatment naïve (TN) or receiving Bruton tyrosine kinase inhibitors (BTKi's) respond to novel adjuvanted vaccines. Understanding the effect of BTKi's on humoral immunity is timely because BTKi's are widely used and vaccination against coronavirus disease 2019 is urgently needed. In 2 open-label, single-arm clinical trials, we measured the effect of BTKi's on de novo immune response against recombinant hepatitis B vaccine (HepB-CpG) and recall response against recombinant zoster vaccine (RZV) in CLL patients who were TN or on BTKi. The primary end point was serologic response to HepB-CpG (anti-hepatitis B surface antibodies ≥10 mIU/mL) and RZV (≥fourfold increase in anti-glycoprotein E). The response rate to HepB-CpG was lower in patients on BTKi (3.8%; 95% confidence interval [CI], 0.7-18.9) than patients who were TN (28.1%; 95% CI, 15.6-45.4; P = .017). In contrast, the response rate to RZV did not differ significantly between the BTKi (41.5%; 95% CI, 27.8-56.6) and TN cohorts (59.1%; 95% CI, 38.7-76.7; P = .2). BTKi's were associated with a decreased de novo immune response following HepB-CpG, whereas recall immune response following RZV was not significantly affected by BTKi therapy. These trials were registered at www.clinicaltrials.gov as #NCT03685708 (Hep-CpG) and #NCT03702231 (RZV). •De novo immune response to hepatitis B vaccine was nearly absent in CLL patients on BTKi and impaired in treatment-naïve patients.•Recall immune response to zoster vaccine was not significantly different between CLL patients on BTKi and treatment-naïve patients. [Display omitted]