Among patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), a third dose of the BNT162b2 mRNA vaccine against COVID-19 may induce an antibody response in nearly one-quarter of patients, according to research published in Blood.

COVID-19, which is caused by the SARS-CoV-2 coronavirus, is known to be more severe in elderly patients and in those with comorbidities. CLL, which is predominantly diagnosed in elderly patients, is a known high-risk comorbidity, and data have shown that patients with CLL are significantly more likely to have serious cases of COVID-19.

Previous research has demonstrated that antibody responses in this patient population are impaired. For this study, researchers evaluated the efficacy of a third BNT162b2 mRNA vaccine dose among patients with CLL/SLL who did not respond to an initial 2-dose regimen.

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Overall, 172 patients were included. The median age at third vaccination dose was 72.1 years, 69.9% of patients were male sex, and 58.1% of patients were on active anticancer therapy.

In the overall cohort, the antibody response rate was 23.8%. Patients who were treatment-naïve (16 of 40 patients; 40%) or who were not receiving active therapy (13 of 32 patients; 40.6%) were more likely to have a response (odds ratio [OR], 4.9 and 5.0, respectively; both P <.001) than were those actively receiving therapy (12 of 100 patients; 12%).

Patients receiving a Bruton kinase inhibitor (9 of 59 patients; 15.3%) or venetoclax with or without an anti-CD20 antibody (3 of 39 patients; 7.7%) had a very low likelihood of response.

Multivariate analysis showed that no active therapy (OR, 5.6; P <.001) and immunoglobulin A levels greater than 80 mg/dL (OR, 5.8; P <.001) were both predictive of an antibody response.

“These findings are of practical importance because they show that a third dose can still achieve seroconversion even in the more immunosuppressed subgroup of patients with CLL,” the authors wrote.

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Herishanu Y, Rahav G, Levi S, et al. Efficacy of a third BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL who failed standard 2-dose vaccination. Blood. 2022;139(5):678-685. doi:10.1182/blood.2021014085