Prospective comprehensive profiling of immune responses to COVID‐19 vaccination in patients on zanubrutinib therapy

Abstract

Zanubrutinib‐treated and treatment‐naïve patients with chronic lymphocytic leukaemia (CLL) or Waldenstrom's macroglobulinaemia were recruited in this prospective study to comprehensively profile humoral and cellular immune responses to COVID‐19 vaccination. Overall, 45 patients (median 72 years old) were recruited; the majority were male (71%), had CLL (76%) and were on zanubrutinib (78%). Seroconversion rates were 65% and 77% following two and three doses, respectively. CD4+ and CD8+ T‐cell response rates increased with third dose. In zanubrutinib‐treated patients, 86% developed either a humoral or cellular response. Patients on zanubrutinib developed substantial immune responses following two COVID‐19 vaccine doses, which further improved following a third dose.

Local and Systemic Immunity During Five Vaccinations Against SARS-CoV-2 in Zanubrutinib-Treated Patients With Chronic Lymphocytic Leukemia

“…Limited information is available on the impact on serological response under a strong BTK inhibitor such as zanubrutinib. Recently, a seroconversion rate of 77% was reported after three vaccine doses in zanubrutinib-treated patients with CLL or Waldenstrom’s macroglobulinemia using an alternative antibody detection method (even though the levels were not specified in U/mL) [ 13 ]. In the zanubrutinib-treated patients included in the present study, the median Ab level after five vaccine doses as determined by the standardized Elecsys ® assay was only 2.7 U/mL, which was 1,000-fold lower than in age-matched healthy donors, and 43% of tested patients were still seronegative.…”

“…Our small cohort size precluded definitive conclusions about T-cell kinetics, although we found a significant boost in CD8 + T-cell reactivity after dose 3, with no further increase after doses 4 and 5. Also in the three-dose zanubrutinib vaccine report by Nguyen et al, T-cell reactivities were increased by a third dose [ 13 ]. A third-dose boost was also reported in other subsets of patients with CLL [ 19 , 20 ], whereas in lymphoma patients, a Th1, but not CD8 + T cell response, was reported by dose 3 [ 21 ].…”