Patients with chronic lymphocytic leukemia (CLL) demonstrated a lower humoral response to the hepatitis B virus (HBV) and the varicella-zoster virus (VZV) vaccines compared with the general population, according to the results of a prospective trial published in Blood.

Bruton tyrosine kinase (BTK) is an effective target for the treatment of CLL, but it is also involved in B-cell receptor signaling and humoral immunity. “The impact of BTK inhibition on vaccine response has potential implications for vaccination strategies for an increasing number of patients with CLL receiving this therapy,” the authors wrote. The response rate to both vaccines exceeds 95% in the general population.

The analysis included 2 open-label, prospective phase 2 trials that evaluated the efficacy of the HBV vaccine, HepB-CpG, and the recombinant zoster vaccine among 58 and 63 patients, respectively, with CLL who were naive to treatment or undergoing treatment with a BTK inhibitor (ibrutinib or acalabrutinib) for at least 6 months. The vaccines were administered individually, in combination, or sequentially at 0 and 3 months, and titers were measured at baseline and at 6 months. The primary endpoints were achievement of HBV seroprotective titer or seroconversion to VZV anti-glycoprotein E (gE).

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Patients undergoing treatment with a BTK inhibitor demonstrated a lower response to the HBV vaccine compared with treatment-naive patients (3.8% vs 28.1%, respectively; P =.017). Median anti-HBV titers were 0.05 mIlU/mL and 1.30 mIU/mL in the BTK inhibitor and treatment-naive groups, respectively, at 6 months.

There was no significant difference in the response rates to the recombinant zoster vaccine. Response was noted in 41.5% of patients in the BTK inhibitor group vs 59.1% of treatment-naive patients (P =.2).  At 6 months, the serum anti-gE antibody titer was 0.7 in both groups.

Considering the historical 95% response rate to these vaccines among the general population, the authors noted that “these results highlight that vaccine responses are impaired in treatment-naive CLL patients, even with novel adjuvanted formulations.”

The majority of adverse events reported were grade 1 to 2, with the most common being injection-site pain and myalgia. There were no treatment-related serious adverse events reported.


Pleyer C, Ali MR, Cohen JI, et al. Effect of Bruton tyrosine kinase inhibitor on efficacy of adjuvanted recombinant hepatitis B and zoster vaccines. Blood. 2021;137:185-189. doi:10.1182/blood.2020008758