Secondary Immunodeficiency in Hematological Malignancies: Focus on Multiple Myeloma and Chronic Lymphocytic Leukemia

Allegra, Alessandro; Tonacci, Alessandro; Musolino, Caterina; Pioggia, Giovanni; Gangemi, Sebastiano

doi:10.3389/fimmu.2021.738915

Cited by 44 publications

(47 citation statements)

References 261 publications

(285 reference statements)

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“…In addition, hematologic cancer patients with COVID‐19 had a high frequency of severe events like a higher mortality rate and a more severe COVID‐19 course 6 . The immune system dysfunction is one of the main reasons that confirm patients with hematological malignancies are more vulnerable 7 . Moreover, anti‐cancer therapies such as chemotherapy, radiotherapy, and immunosuppressive drugs worsen the condition of these patients 8 .…”

Section: Introductionmentioning

confidence: 99%

“… 6 The immune system dysfunction is one of the main reasons that confirm patients with hematological malignancies are more vulnerable. 7 Moreover, anti‐cancer therapies such as chemotherapy, radiotherapy, and immunosuppressive drugs worsen the condition of these patients. 8 There are a limited number of studies on the prevalence of comorbidities and mortality rate in COVID‐19 patients with hematological malignancies.…”

Section: Introductionmentioning

confidence: 99%

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Comorbidities and mortality rate in COVID‐19 patients with hematological malignancies: A systematic review and meta‐analysis

Naimi

Yashmi

Jebeleh

et al. 2022

Clinical Laboratory Analysis

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comorbidities and mortality rate in COVID‐19 patients with hematological malignancies: A systematic review and meta‐analysis

Naimi

Yashmi

Jebeleh

et al. 2022

Clinical Laboratory Analysis

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“…Multiple myeloma and untreated CLL are associated with immunodeficiencies that hamper vaccination-induced antibody responses. 20 Nevertheless, a 3 rd mRNA-1273 vaccination in these patients led to a significant increase in S1 IgG concentrations, to levels that were no longer significantly different from those obtained in healthy individuals after the standard 2-dose mRNA-1273 schedule. Similar dynamics were observed in patients with myeloproliferative neoplasms on the JAK-2 inhibitor ruxolitinib, patients with AML on hypomethylating therapy and patients with chronic GvHD.…”

Section: Discussionmentioning

confidence: 68%

“…17,18 Reduced vaccine immunogenicity in hematology patients is related to the disease itself and the therapy thereof. 19,20 We prospectively measured antibody responses to mRNA-1273 (Moderna/Spikevax) vaccination in those hematology patients that are generally considered too immunocompromised to mount an effective immune response and in whom vaccinations are often postponed until (later) after treatment. 12,21,22 In collaboration with a number of other prospective cohort studies on the immunogenicity of COVID-19 vaccination among immunocompromised and healthy individuals conducted in the Netherlands we quantified antibody concentrations against the WHO standard and set a spike-1 (S1) IgG concentration of 300 BAU/ml as the lower threshold of an adequate COVID-19 vaccine response.…”

Section: Introductionmentioning

confidence: 99%

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Three-dose mRNA-1273 vaccination schedule: sufficient antibody response in majority of immunocompromised hematology patients

Haggenburg

Hofsink

Lissenberg‐Witte

et al. 2022

Preprint

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Importance In patients with hematologic malignancies, the immunogenicity of the standard 2-dose mRNA-1273 coronavirus disease 19 (COVID-19) vaccination schedule is often insufficient due to underlying disease and current or recent therapy. Objective To determine whether a 3rd mRNA-1273 vaccination raises antibody concentrations in immunocompromised hematology patients to levels obtained in healthy individuals after the standard 2-dose mRNA-1273 vaccination schedule. Design Prospective observational cohort study. Setting Four academic hospitals in the Netherlands. Participants 584 evaluable immunocompromised hematology patients, all grouped in predefined cohorts spanning the spectrum of hematologic malignancies. Exposure One additional vaccination with mRNA-1273 5 months after completion of the standard 2-dose mRNA-1273 vaccination schedule. Main Outcomes and Measures Serum IgG antibodies to spike subunit 1 (S1) antigens prior to and 4 weeks after each vaccination, and pseudovirus neutralization of wildtype, delta and omicron variants in a subgroup of patients. Results In immunocompromised hematology patients, a 3rd mRNA-1273 vaccination led to median S1 IgG concentrations comparable to concentrations obtained by healthy individuals after the 2-dose mRNA-1273 schedule. The rise in S1 IgG concentration after the 3rd vaccination was most pronounced in patients with a recovering immune system, but potent responses were also observed in patients with persistent immunodeficiencies. Specifically, patients with myeloid malignancies or multiple myeloma, and recipients of autologous or allogeneic hematopoietic cell transplantation (HCT) reached median S1 IgG concentrations similar to those obtained by healthy individuals after a 2-dose schedule. Patients on or shortly after rituximab therapy, CD19-directed chimeric antigen receptor T cell therapy recipients, and chronic lymphocytic leukemia patients on ibrutinib were less or unresponsive to the 3rd vaccination. In the 27 patients who received cell therapy between the 2nd and 3rd vaccination, S1 antibodies were preserved, but a 3rd mRNA-1273 vaccination did not significantly enhance S1 IgG concentrations except for multiple myeloma patients receiving autologous HCT. A 3rd vaccination significantly improved neutralization capacity per antibody. Conclusions and Relevance The primary schedule for immunocompromised patients with hematologic malignancies should be supplemented with a delayed 3rd vaccination. B cell lymphoma patients and allogeneic HCT recipients need to be revaccinated after treatment or transplantation. Trial Registration EudraCT 2021-001072-41

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Antibody Response in Immunocompromised Patients With Hematologic Cancers Who Received a 3-Dose mRNA-1273 Vaccination Schedule for COVID-19

et al. 2022

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IMPORTANCEIt has become common practice to offer immunocompromised patients with hematologic cancers a third COVID-19 vaccination dose, but data substantiating this are scarce.OBJECTIVE To assess whether a third mRNA-1273 vaccination is associated with increased neutralizing antibody concentrations in immunocompromised patients with hematologic cancers comparable to levels obtained in healthy individuals after the standard 2-dose mRNA-1273 vaccination schedule. DESIGN, SETTING, AND PARTICIPANTSThis prospective observational cohort study was conducted at 4 university hospitals in the Netherlands and included 584 evaluable patients spanning the spectrum of hematologic cancers and 44 randomly selected age-matched adults without malignant or immunodeficient comorbidities.EXPOSURES One additional mRNA-1273 vaccination 5 months after completion of the standard 2-dose mRNA-1273 vaccination schedule. Serum immunoglobulin G (IgG) antibodies to spike subunit 1 (S1) antigens prior to and 4 weeks after a third mRNA-1273 vaccination, and antibody neutralization capacity of wild-type, Delta, and Omicron variants in a subgroup of patients. MAIN OUTCOMES AND MEASURES RESULTSIn this cohort of 584 immunocompromised patients with hematologic cancers (mean [SD] age, 60 [11.2] years; 216 [37.0%] women), a third mRNA-1273 vaccination was associated with median S1-IgG concentrations comparable to concentrations obtained by healthy individuals after the 2-dose mRNA-1273 schedule. The rise in S1-IgG concentration after the third vaccination was most pronounced in patients with a recovering immune system, but potent responses were also observed in patients with persistent immunodeficiencies. Specifically, patients with myeloid cancers or multiple myeloma and recipients of autologous or allogeneic hematopoietic cell transplantation (HCT) reached median S1-IgG concentrations similar to those obtained by healthy individuals after a 2-dose schedule. Patients receiving or shortly after completing anti-CD20 therapy, CD19-directed chimeric antigen receptor T-cell therapy recipients, and patients with chronic lymphocytic leukemia receiving ibrutinib were less responsive or unresponsive to the third vaccination. In the 27 patients who received cell therapy between the second and third vaccination, S1 antibodies were preserved, but a third mRNA-1273 vaccination was not associated with significantly enhanced S1-IgG concentrations except for patients with multiple myeloma receiving autologous HCT. A third vaccination was associated with significantly improved neutralization capacity per antibody. CONCLUSIONS AND RELEVANCEResults of this cohort study support that the primary schedule for immunocompromised patients with hematologic cancers should be supplemented with a delayed third vaccination. Patients with B-cell lymphoma and allogeneic HCT recipients need to be revaccinated after treatment or transplantation.

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Secondary Immunodeficiency in Hematological Malignancies: Focus on Multiple Myeloma and Chronic Lymphocytic Leukemia

Cited by 44 publications

References 261 publications

Comorbidities and mortality rate in COVID‐19 patients with hematological malignancies: A systematic review and meta‐analysis

Comorbidities and mortality rate in COVID‐19 patients with hematological malignancies: A systematic review and meta‐analysis

Three-dose mRNA-1273 vaccination schedule: sufficient antibody response in majority of immunocompromised hematology patients

Antibody Response in Immunocompromised Patients With Hematologic Cancers Who Received a 3-Dose mRNA-1273 Vaccination Schedule for COVID-19

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