Prolonged in‐hospital stay and higher mortality after Covid‐19 among patients with <scp>non‐Hodgkin</scp> lymphoma treated with B‐cell depleting immunotherapy

Duléry, Rémy; Lamure, Sylvain; Delord, Marc; Blasi, Roberta Di; Chauchet, Adrien; Hueso, Thomas; Rossi, Cédric; Drénou, Bernard; Deau‐Fischer, Bénédicte; Soussain, Carole; Feugier, Pierre; Noël, Nicolas; Choquet, Sylvain; Bologna, Serge; Joly, Bertrand; Philippe, Laure; Kohn, Milena; Malak, Sandra; Fouquet, Guillemette; Daguindau, Étienne; Taoufik, Yassine; Lacombe, Karine; Cartron, Guillaume; Thiéblemont, Catherine; Besson, Caroline

doi:10.1002/ajh.26209

Cited by 124 publications

(134 citation statements)

References 49 publications

(159 reference statements)

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“…A meta-analysis, including 3377 adult patients with these diseases, reported a 34% risk of death in those suffering from COVID-19 [ 1 ]. Furthermore, B-cell depleting immunotherapy has been associated with prolonged in-hospital stay and higher mortality after COVID19 [ 2 ]. Therefore, patients with hematologic malignancies have been prioritized for primary prevention of COVID-19 with vaccination.…”

Section: Introductionmentioning

confidence: 99%

Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies

et al. 2021

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This study evaluated the safety and immunogenicity of BNT162b2 vaccine in patients with hematological malignancies. Antibodies blocking spike binding to immobilized ACE-2 (NAb) correlated with anti-Spike (S) IgG d42 titers (Spearman r = 0.865, p < 0.0001), and an anti-S IgG d42 level ≥3100 UA/mL was predictive of NAb ≥ 30%, the positivity cutoff for NAb (p < 0.0001). Only 47% of the patients achieved an anti-S IgG d42 level ≥3100 UA/mL after the two BNT162b2 inocula, compared to 87% of healthy controls. In multivariable analysis, male patients, use of B-cell targeting treatment within the last 12 months prior to vaccination, and CD19+ B-cell level <120/uL, were associated with a significantly decreased probability of achieving a protective anti-S IgG level after the second BNT162b2 inoculum. Finally, using the IFN-γ ELISPOT assay, we found a significant increase in T-cell response against the S protein, with 53% of patients having an anti-S IgG-positive ELISPOT after the second BNT162b2 inoculum. There was a correlation between the anti-S ELISPOT response and IgG d42 level (Spearman r = 0.3026, p = 0.012). These findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with hematological malignancies, but only around half of the patients can likely achieve effective immune protection against COVID-19.

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Section: Introductionmentioning

confidence: 99%

Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies

et al. 2021

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Section: Introductionmentioning

confidence: 99%

“…Individuals with underlying autoimmune conditions, including multiple sclerosis (MS), and those on immune-modulatory therapies were not included in these phase 3 clinical trials. As a result, the magnitude and quality of immune response to mRNA vaccination is not well characterized in these potentially vulnerable patient populations that may be at risk for higher COVID-19 associated morbidity and mortality, and more prone to infect others [6][7][8][9][10][11][12] .Anti-CD20 antibody (aCD20) based B cell depleting strategies are implemented in hematologic malignancies 13 and across a variety of autoimmune disorders 14 , including MS 15,16 , with high rates of success. Upon antigen exposure, B cells have the ability to form memory cells or differentiate into plasmablasts and plasma cells 17 .…”

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confidence: 99%

Altered cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy

Apostolidis

Kakara

Painter

et al. 2021

Preprint

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SARS-CoV-2 mRNA vaccination in healthy individuals generates effective immune protection against COVID-19. Little is known, however, about the SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses in patients with multiple sclerosis on anti-CD20 (MS-aCD20) monotherapy following SARS-CoV-2 mRNA vaccination. Treatment with aCD20 significantly reduced Spike and RBD specific antibody and memory B cell responses in most patients, an effect that was ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. In contrast, all MS-aCD20 patients generated antigen-specific CD4 and CD8 T-cell responses following vaccination. However, treatment with aCD20 skewed these responses compromising circulating Tfh responses and augmenting CD8 T cell induction, while largely preserving Th1 priming. These data also revealed underlying features of coordinated immune responses following mRNA vaccination. Specifically, the MS-aCD20 patients who failed to generate anti-RBD IgG had the most severe defect in cTfh cell responses and more robust CD8 T cell responses compared to those who generated anti-RBD IgG, whose T cell responses were more similar to healthy controls. These data define the nature of SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients, and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making, patient education and public health policy for patients treated with aCD20 and other immunosuppressed patients.

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“…In contrast, several of the seronegative patients showed an emerging cellular response after dose 3, suggesting a positive effect of a second booster dose despite the absence of humoral response. Given the importance of a T-cell response in critically ill COVID-19 patients (14)(15), this is another expected benefit of the dose 3 vaccine dose, especially for patients treated with anti-CD20 Mab based therapy who are at high risk for death or ongoing SARS-CoV-2 shedding (16)(17).…”

Section: Discussionmentioning

confidence: 99%

Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients treated for lymphoid malignancies

Ré

Seitz-Polski

Carlès

et al. 2021

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Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients treated for lymphoid malignancies. BACKGROUND: Immunocompromised patients such as patients with hematological malignancies have impaired immune response to two doses of BNT162b2 (Pfizer / BioNtech) vaccine against SARS-CoV-2. Evaluation of a repeated immune stimulation with a third vaccine dose is needed. METHODS: a vaccine monitoring observatory was conducted in outpatients who were treated for lymphoid malignancies (LM) to monitor both immune and cellular response measured the day of administration of the dose 3 of the mRNA vaccine BNT162b2 and again three to four weeks. Elecsys Anti-SARS-CoV-2 immunoassay was used to asses to the level of SARS-CoV-2 anti-Spike (S) antibodies (Abs) titer and SARS-CoV-2-specific T-cell responses were assessed by a whole blood Interferon-Gamma Release Immuno Assay (IGRA) (QuantiFERON Human IFN-gamma SARS-CoV-2, Qiagen). RESULTS: Among the 43 assessable patients (suffering from chronic lymphocytic leukemia (CLL) (n=15), indolent and aggressive B cell non-Hodgkin lymphoma (NHL) (n=14), and multiple myeloma (MM) (n=16)), 18 (41,8%) had no anti-S Abs before the dose 3 of BNT162b2 vaccine (n=9 CLL, n=8 NHL, n=1 MM), and they all 18 remained negative after the dose 3. Amongst the 25 patients with positive anti-S titers before dose 3, all patients remained positive and 23 patients increased their anti-S titer after dose 3. Patients with CLL and/or with previous anti-CD20 therapy treated within 12 months of administration of dose 3 had no significant increase of the humoral response. Among 22 available patients, dose 3 of BNT162b2 vaccine significantly increased the median IFN-gamma secretion. On eight (36.4%) patients who were double-negative for both immune and cellular response, five (22.7%) patients remained double-negative after dose 3. CONCLUSIONS Dose 3 of BNT162b2 vaccine stimulated humoral immune response among patients with LM, in particular patients with MM (who had higher anti-S baseline titer after dose 2) and those with no anti-CD20 treatment history within a year. T-cell response was increased among patients in particular with no active chemotherapy regimen. Our data support the use of an early third vaccine dose among immunocompromised patients followed for LM though some of them will still have vaccine failure.

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Prolonged in‐hospital stay and higher mortality after Covid‐19 among patients with non‐Hodgkin lymphoma treated with B‐cell depleting immunotherapy

Cited by 124 publications

References 49 publications

Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies

Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies

Altered cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy

Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients treated for lymphoid malignancies

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