Response to COVID-19 mRNA vaccination in multiple myeloma is conserved but impaired compared to controls

Bitoun, Samuel; Henry, J.; Vauloup‐Fellous, Christelle; Dib, Nicolas; Belkhir, Rakiba; Mouna, Lina; Joly, Charles-Alexandre; Desjardins, Delphine; Bitu, Marie; Grand, Roger Le; Séror, Raphaèle; Afonso, Anne-Marie Roque; Mariette, Xavier

doi:10.1186/s13045-021-01183-2

Cited by 26 publications

(26 citation statements)

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“…The rate of antibody non-responders after the first dose was highest in patients with MM (50%) and SOT (28.6%), but improved four weeks after the second dose to 17.1% and 1.6%, respectively. These results underline the importance of completing the two-dose schedule with mRNA vaccines and are in line with data showing diminished seroresponses within one month after the second dose in MM and SOT patients compared to controls ( 18 – 20 ). Of note, patients with hematooncological cancers such as MM have seroconversion rates compared to SOT patients.…”

Section: Discussionsupporting

confidence: 89%

SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients – A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel Disease

et al. 2022

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BackgroundIndividuals with secondary immunodeficiencies belong to the most vulnerable groups to succumb to COVID-19 and thus are prioritized for SARS-CoV-2 vaccination. However, knowledge about the persistence and anamnestic responses following SARS-CoV-2-mRNA vaccinations is limited in these patients.MethodsIn a prospective, open-label, phase four trial we analyzed S1-specific IgG, neutralizing antibodies and cytokine responses in previously non-infected patients with cancer or autoimmune disease during primary mRNA vaccination and up to one month after booster.Results263 patients with solid tumors (SOT, n=63), multiple myeloma (MM, n=70), inflammatory bowel diseases (IBD, n=130) and 66 controls were analyzed. One month after the two-dose primary vaccination the highest non-responder rate was associated with lower CD19+ B-cell counts and was found in MM patients (17%). S1-specific IgG levels correlated with IL-2 and IFN-γ responses in controls and IBD patients, but not in cancer patients. Six months after the second dose, 18% of patients with MM, 10% with SOT and 4% with IBD became seronegative; no one from the control group became negative. However, in IBD patients treated with TNF-α inhibitors, antibody levels declined more rapidly than in controls. Overall, vaccination with mRNA-1273 led to higher antibody levels than with BNT162b2. Importantly, booster vaccination increased antibody levels >8-fold in seroresponders and induced anamnestic responses even in those with undetectable pre-booster antibody levels. Nevertheless, in IBD patients with TNF-α inhibitors even after booster vaccination, antibody levels were lower than in untreated IBD patients and controls.ConclusionImmunomonitoring of vaccine-specific antibody and cellular responses seems advisable to identify vaccination failures and consequently establishing personalized vaccination schedules, including shorter booster intervals, and helps to improve vaccine effectiveness in all patients with secondary immunodeficiencies.Trial registrationEudraCT Number: 2021-000291-11

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Section: Discussionsupporting

confidence: 89%

SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients – A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel Disease

et al. 2022

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“…Overall, 82 studies were included for meta-analysis ( table 1 , supplementary table 2). 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 …”

Section: Resultsmentioning

confidence: 99%

Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis

Lee

Wong

Chai

et al. 2022

BMJ

348

313

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Objective To compare the efficacy of covid-19 vaccines between immunocompromised and immunocompetent people. Design Systematic review and meta-analysis. Data sources PubMed, Embase, Central Register of Controlled Trials, COVID-19 Open Research Dataset Challenge (CORD-19), and WHO covid-19 databases for studies published between 1 December 2020 and 5 November 2021. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched in November 2021 to identify registered but as yet unpublished or ongoing studies. Study selection Prospective observational studies comparing the efficacy of covid-19 vaccination in immunocompromised and immunocompetent participants. Methods A frequentist random effects meta-analysis was used to separately pool relative and absolute risks of seroconversion after the first and second doses of a covid-19 vaccine. Systematic review without meta-analysis of SARS-CoV-2 antibody titre levels was performed after first, second, and third vaccine doses and the seroconversion rate after a third dose. Risk of bias and certainty of evidence were assessed. Results 82 studies were included in the meta-analysis. Of these studies, 77 (94%) used mRNA vaccines, 16 (20%) viral vector vaccines, and 4 (5%) inactivated whole virus vaccines. 63 studies were assessed to be at low risk of bias and 19 at moderate risk of bias. After one vaccine dose, seroconversion was about half as likely in patients with haematological cancers (risk ratio 0.40, 95% confidence interval 0.32 to 0.50, I 2 =80%; absolute risk 0.29, 95% confidence interval 0.20 to 0.40, I 2 =89%), immune mediated inflammatory disorders (0.53, 0.39 to 0.71, I 2 =89%; 0.29, 0.11 to 0.58, I 2 =97%), and solid cancers (0.55, 0.46 to 0.65, I 2 =78%; 0.44, 0.36 to 0.53, I 2 =84%) compared with immunocompetent controls, whereas organ transplant recipients were 16 times less likely to seroconvert (0.06, 0.04 to 0.09, I 2 =0%; 0.06, 0.04 to 0.08, I 2 =0%). After a second dose, seroconversion remained least likely in transplant recipients (0.39, 0.32 to 0.46, I 2 =92%; 0.35, 0.26 to 0.46), with only a third achieving seroconversion. Seroconversion was increasingly likely in patients with haematological cancers (0.63, 0.57 to 0.69, I 2 =88%; 0.62, 0.54 to 0.70, I 2 =90%), immune mediated inflammatory disorders (0.75, 0.69 to 0.82, I 2 =92%; 0.77, 0.66 to 0.85, I 2 =93%), and solid cancers (0.90, 0.88 to 0.93, I 2 =51%; 0.89, 0.86 to 0.91, I 2 =49%). Seroconversion was similar between people with HIV and immunocompetent controls (1.00, 0.98 to 1.01, I 2 =0%; 0.97, 0.83 to 1.00, I 2 =89%). Systematic review of 11 studies showed that a third dose of a covid-19 mRNA vaccine was associated with seroconversion among vaccine non-responders with solid cancers, haematological cancers, and immune mediated inflammatory disorders, although response was variable in transplant recipients and inadequately studied in people with HIV and those receiving non-mRNA vaccines. Conclusion Seroconversion rates after covid-19 vaccination were significantly lower in immunocompromised patients, especially organ transplant recipients. A second dose was associated with consistently improved seroconversion across all patient groups, albeit at a lower magnitude for organ transplant recipients. Targeted interventions for immunocompromised patients, including a third (booster) dose, should be performed. Systematic review registration PROSPERO CRD42021272088.

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“…Eleven studies reported specific outcomes for patients in remission 11 , 16-18 , 21-25 , 30 , 31 ( Supplementary Table S2 ). In the pooled analysis of these studies, the patients in remission had lower seroconversion rates than healthy controls, although with a smaller RD (RD: −0.10%, 95% CI: −0.18%, −0.02%, P = .01; Fig.…”

Section: Resultsmentioning

confidence: 99%

Impact of Therapy in Patients with Hematologic Malignancies on Seroconversion Rates After SARS-CoV-2 Vaccination

et al. 2022

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Introduction The leading professional organizations in the field of hematology have recommended severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) vaccination for all patients with hematologic malignancies notwithstanding efficacy concerns. Here we report a systematic literature review regarding the antibody response to SARS-CoV-2 vaccination in patients with hematologic malignancies and its key determinants. Methods We conducted a systematic search of original articles evaluating the seroconversion rates with SARS-CoV-2 vaccines in hematological malignancies from the PubMed database published between April 1, 2021 and December 4, 2021. Calculated risk differences (RD) and 95% confidence intervals (CI) to compare seroconversion rates between patients with hematologic malignancies versus healthy control subjects used the Review Manager software, version 5.3. Results In our meta-analysis, we included 26 studies with control arms. After the first dose of vaccination, patients with hematologic malignancies had significantly lower seroconversion rates than controls (33.3% vs 74.9%; RD: −0.48%, 95% CI: −0.60%, −0.36%, P < .001). The seroconversion rates increased after the second dose, although a significant difference remained between these 2 groups (65.3% vs 97.8%; RD: −0.35%, 95% CI: −0.42%, −0.28%, P < .001). This difference in seroconversion rates was particularly pronounced for Chronic Lymphocytic Leukemia (CLL) patients (RD: −0.46%, 95% CI: −0.56, −0.37, P < .001), and for patients with B-lineage leukemia/lymphoma treated with anti-CD20 antibodies (RD: −0.70%, 95% CI: −0.88%, −0.51%, P < .001) or Bruton Tyrosine Kinase Inhibitors (BTKi; RD: −0.63%, 95% CI: −0.85%, −0.41%, P < .001). The RD was lower for patients under remission (RD: −0.10%, 95% CI: −0.18%, −0.02%, P = .01). Conclusion The seroconversion rates following SARS-CoV-2 vaccination in patients with hematologic malignancies, especially in CLL patients and patients treated with anti-CD20 antibodies or BTKi, were significantly lower than the seroconversion rates in healthy control subjects. Effective strategies capable of improving vaccine efficacy in these vulnerable patient populations are urgently needed.

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Response to COVID-19 mRNA vaccination in multiple myeloma is conserved but impaired compared to controls

Cited by 26 publications

References 4 publications

SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients – A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel Disease

SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients – A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel Disease

Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis

Impact of Therapy in Patients with Hematologic Malignancies on Seroconversion Rates After SARS-CoV-2 Vaccination

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