key: cord-0718983-u5a1gibh
authors: Gressens, Simon B.; Fourati, Slim; Le Bouter, Anne; Le Bras, Fabien; Dupuis, Jehan; Hammoud, Mohammad; El Gnaoui, Taoufik; Gounot, Romain; Roulin, Louise; Belhadj, Karim; Haioun, Corinne; Gallien, Sébastien; Melica, Giovanna; Lemonnier, François
title: Anti-SARS-CoV-2 antibody response after 2 and 3 doses of BNT162b2 mRNA vaccine in patients with lymphoid malignancies
date: 2022-03-05
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2022.02.029
sha: c074a5d9f19160a585ea80c8b0dc6369c933effb
doc_id: 718983
cord_uid: u5a1gibh

OBJECTIVES: COVID-19 patients affected by hematological malignancies have a more severe course of the disease and higher mortality, prompting for effective prophylaxis. The present study aims to evaluate the humoral response after mRNA vaccination as well as the impact of a third vaccine dose in patients with lymphoid malignancies. METHODS: We conducted a single center study, evaluating the serological responses of mRNA vaccination amongst a cohort of 200 patients affected by lymphoid malignancies after two or three doses using an industrial SARS-CoV-2 serology assay for anti-RBD Spike IgG detection and quantification. RESULTS: Among patients with plasma cell disorders, 59/96 (61%) had a seroconversion (anti-RBD > 50 AU/mL), and recent anti-CD38 therapies were associated with lower serological anti-RBD IgG concentrations (median IgG concentration 137 (IQR 0-512) AU/mL vs 543 (IQR 35-3496) AU/mL, p<0.001). Patients with B-cell malignancies had a lower seroconversion rate (20/84, 24%) mainly due to the broad usage of anti-CD20 monoclonal antibodies, only 2/53 (4%) patients treated by anti-CD20 antibodies during the last 12 months experienced a seroconversion. A total of 78 patients (44 with plasma cell disorders, 27 with B-cell malignancies and 7 with other lymphomas) received a third dose of vaccine. The seroconversion rate and antibody concentrations increased significantly, especially in patients with plasma cell disorders where an increment of anti-RBD IgG concentrations was observed in 31/44 (70%) of the patients, with an anti-RBD concentration median-fold increase of 10.6 (IQR 2.4-25.5), while its benefit in B-cell malignancies is uncertain, only 2/25 (8%) patients having seroconverted after the vaccine booster, without increased median antibody concentration. CONCLUSIONS: A third mRNA vaccine dose improved significantly humoral responses among patients with plasma cell disorders, while the effect was limited among patients with B-cell malignancies.

Early in the COVID-19 pandemic a more severe course of the disease and higher mortality were 57 reported among patients with malignant hemopathies [1] . Current French guidelines advise a 58 third dose with prioritization to immunocompromised recipients [2] . A third dose of vaccine in 59 solid organ transplant recipients was able to significantly improve its immunogenicity[3], but 60 available data among hematological patients remain scarce and incomplete. Previous reports 61

showed particularly low response rates (especially with anti-CD20 therapy) among patients with 62 lymphoid malignancies, and the effect of treatment such as anti-plasma cell drugs remains 63 controversial [4] . Here, we report the anti-SARS COV-2 antibody (anti-receptor binding domain 64 (RBD) IgG) response in vaccinated patients with lymphoid hematological malignancies in a 65 tertiary center, and immunogenicity of a third dose as boost in a subgroup of this population. 66 J o u r n a l P r e -p r o o f

We conducted a single center cohort study evaluating immunological responses among patients 68 treated for lymphoid malignancies in a tertiary center. All patients with an active follow-up in 69 our center were offered an on-site vaccination by BNT162b2 mRNA vaccine since January 1 st 70 2021 (2 injections scheduled 21 days apart). Since March 2021, patients were advised to receive 71 a third injection of vaccine. Humoral response was evaluated by SARS-CoV-2 serology using the 72 IgG II Quant Assay (Abbot Laboratories, Wiesbaden, Germany) for anti-RBD Spike (S) IgG 73 detection and quantification. A quantifiable anti-RBD IgG concentration above the 74 manufacturer defined threshold (50 AU/mL) was considered as seroconversion. We stratified 75 samples by anti-RBD IgG concentrations above or below 1000 AU/mL and 4160 AU/mL, 76 associated with a high probability of virus neutralization in in-vitro plaque reduction assays 77 against several variants of concern[5,6]. The study was approved by local ethics committee and 78 in accordance with the 1964 Helsinki declaration. Categorical variables were expressed as 79 percentages, quantitative variables as median (interquartile range, IQR). Statistical comparisons 80 were performed using the Wilcoxon test and the Kruskal-Wallis non-parametric tests as 81 appropriate. Additional details regarding immunological response evaluation, statistics and 82 ethics are available in the Supplemental appendix. 83 J o u r n a l P r e -p r o o f

The study included a total of 200 non-selected patients consecutively followed in our center 85 between January 1 st 2021 and July 14 th 2021. Baseline characteristics are shown in Table 1 . 86 Seroconversion rate ranged from 3/20 (15%) patients with follicular lymphoma to 8/9 (89%) in 87

Hodgkin lymphoma patients ( Figure 1A ). Aiming to assess factors affecting vaccine response, 88 we clustered lymphoid diseases into groups based on common ontogeny and treatment type. with or without such treatment respectively (p=0.07)), but fewer patients reached the 100 thresholds of 1000 (10/54 (19%) vs 18/48 (43%), p=0.005) and 4160 AU/mL (4/54 (7%) vs 11/42 101 (26%), p=0.008). 102

In the 84 patients with BCM, 20/84 (24%) seroconverted and the median anti-RBD 103 concentration was 0 (IQR 0-40) AU/mL ( Figure 1B ). We observed a seroconversion in 18/31 104 but only in 1/46 (2%) patients who received anti-CD20 antibodies in the last 6 months (with 106 anti-RBD concentration <1000 AU/mL). Although limited by a small number of patients, a 107 similar magnitude of seroconversion was observed when anti-CD20 was administered 6 to 12 108 months before vaccination (1/7 (14%) p=0.7). On the other hand, 7/10 (70%) patients who 109 received at least one vaccine dose before starting any treatment (n=10) had a seroconversion, 110 the median time before treatment being 16 days (IQR 5-29). 111

In a multivariate analysis, factors affecting vaccine humoral response in patients with lymphoid 112 malignancies were age (p<0.001), number of prior lines of therapy (p=0.01) and recent 113 treatment by anti-CD20/CD38 antibodies (<12 months) (p=0.007) (supplemental Table) . 

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