Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia

Abstract

Patients with chronic lymphocytic leukemia (CLL) have an increased risk for severe COVID-19 disease and mortality. The goal of this study was to determine the efficacy of COVID-19 vaccine in patients with CLL. We evaluated humoral immune responses to the BNT162b2 messenger RNA (mRNA) COVID-19 vaccine in patients with CLL and compared responses with those obtained in age-matched healthy control subjects. Patients received 2 vaccine doses, 21 days apart, and antibody titers were measured by using the Elecsys Anti-SARS-CoV-2 S assay after administration of the second dose. In a total of 167 patients with CLL, the antibody response rate was 39.5%. A comparison between 52 patients with CLL and 52 sex- and aged-matched healthy control subjects revealed a significantly reduced response rate among patients (52% vs 100%, respectively; adjusted odds ratio, 0.010; 95% confidence interval, 0.001-0.162; P < .001). The response rate was highest in patients who obtained clinical remission after treatment (79.2%), followed by 55.2% in treatment-naive patients and 16.0% in patients under treatment at the time of vaccination. In patients treated with either Bruton's tyrosine kinase inhibitors or venetoclax ± anti-CD20 antibody, response rates were considerably low (16.0% and 13.6%). None of the patients exposed to anti-CD20 antibodies <12 months before vaccination responded. In a multivariate analysis, the independent predictors of response were younger age, female sex, lack of currently active treatment, immunoglobulin G levels ≥550 mg/dL, and immunoglobulin M levels ≥40 mg/dL. In conclusion, antibody-mediated response to the BNT162b2 mRNA COVID-19 vaccine in patients with CLL is markedly impaired and affected by disease activity and treatment. This trial was registered at www.clinicaltrials.gov as #NCT04746092.

Keywords: BNT162b2; CLL; COVID-19 vaccine; NEOPLASIA/Lymphoid leukemias; antibody response.

Graphical abstract

Figure 1.

Anti–SARS-CoV-2 antibody response in patients with CLL and healthy control subjects. (A-B) Distribution of individual responses in patients with CLL (n = 52) and sex- and age-matched control subjects (n = 52). Each column represents the level of antibodies in individual patients (red bars indicate treatment naive, green bar indicates on-therapy, blue bars indicate off-therapy in remission, and purple bars indicate off-therapy in relapse) in panel A and in individual healthy control subjects (red bars) in panel B. (C) Response rate in patients with CLL (n = 52) and sex- and age-matched control subjects (n = 52). (D) Anti–SARS-CoV-2 antibody levels in patients with CLL (n = 52) and sex- and age-matched control subjects (n = 52).

Figure 2.

Anti–SARS-CoV-2 antibody responses in patients with CLL according to disease status and treatment. (A-B) Response rate and anti–SARS-CoV-2 antibody levels in patients with CLL according to disease status: Treatment naive (n = 58), on-therapy (n = 75), off-therapy in remission (n = 24), and off-therapy in relapse (n = 10). (C) Response rate in patients with CLL treated with BTKi (n = 50) and venetoclax (Ven) ± anti-CD20 antibody (n = 22). NS, not significant.

Figure 3.

Local and systemic reactions reported after injection of BNT162b2 in patients with CLL (N = 167). Reactions reported after the first vaccine dose (A) and after the second vaccine dose (B).