Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with B-cell non-Hodgkin lymphoma

Abstract

Patients diagnosed with B-cell non-Hodgkin lymphoma (B-NHL), particularly if recently treated with anti-CD20 antibodies, are at risk of severe COVID-19 disease. Because studies evaluating humoral response to COVID-19 vaccine in these patients are lacking, recommendations regarding vaccination strategy remain unclear. The humoral immune response to BNT162b2 messenger RNA (mRNA) COVID-19 vaccine was evaluated in patients with B-NHL who received 2 vaccine doses 21 days apart and compared with the response in healthy controls. Antibody titer, measured by the Elecsys Anti-SARS-CoV-2S assay, was evaluated 2 to 3 weeks after the second vaccine dose. Patients with B-NHL (n = 149), aggressive B-NHL (a-B-NHL; 47%), or indolent B-NHL (i-B-NHL; 53%) were evaluated. Twenty-eight (19%) were treatment naïve, 37% were actively treated with a rituximab/obinutuzumab (R/Obi)-based induction regimen or R/Obi maintenance, and 44% had last been treated with R/Obi >6 months before vaccination. A seropositive response was achieved in 89%, 7.3%, and 66.7%, respectively, with response rates of 49% in patients with B-NHL vs 98.5% in 65 healthy controls (P < .001). Multivariate analysis revealed that longer time since exposure to R/Obi and absolute lymphocyte count ≥0.9 × 103/μL predicted a positive serological response. Median time to achieve positive serology among anti-CD20 antibody-treated patients was longer in i-B-NHL vs a-B-NHL. The humoral response to BNT162b2 mRNA COVID-19 vaccine is impaired in patients with B-NHL who are undergoing R/Obi treatment. Longer time since exposure to R/Obi is associated with improved response rates to the COVID-19 vaccine. This study is registered at www.clinicaltrials.gov as #NCT04746092.

Graphical abstract

Figure 1.

Serological response rates to COVID-19 vaccine. (A) Percentage of response rates in patients with B-NHL vs age-compatible, healthy controls. (B) Median values and range of anti-SARS-CoV-2 Ab titer levels in patients with B-NHL vs healthy controls. Mean titers ± standard deviation for each group are presented. (C-D) Distribution of anti-SARS-CoV-2 Ab titer levels among B-NHL patients and healthy controls. In panel C, each bar represents 1 patient with B-NHL, in panel D, each bar represents 1 healthy control.

Figure 2.

Serological response rates in subgroups of patients with B-NHL. (A) The percentage of seropositive patients in each of the B-NHL patient subgroups: post treatment (patients who completed anti-CD20 Ab containing therapy >6 months before vaccination), active treatment (patients who are under current anti-CD20 Ab therapy or that completed treatment up to 6 months before vaccination), and treatment naïve (patients with i-B-NHL under watch-and-wait management), compared with healthy controls. (B) Shown are titer levels in each of the B-NHL patient subgroups and in healthy controls.

Figure 3.

A longer time since last exposure to anti-CD20 Abs is associated with increased seropositivity rates. (A) Hazard ratio (HR) to achieve positive anti-SARS-CoV-2 serology in all patients with B-NHL who were exposed to anti-CD20 Abs is plotted against months from last exposure to anti-CD20 Abs, using a Kaplan-Meier HR curve. (B) HR to achieve positive anti-SARS-CoV-2 serology in patients with a-B-NHL and i-B-NHL who were exposed to anti-CD20 Abs is plotted against months since last exposure to anti-CD20 Abs, using a Kaplan-Meier HR curve.

Figure 4.

AEs of COVID-19 vaccine in patients with B-NHL vs healthy controls.