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Immunogenicity of Covid-19 Vaccination for Patients With Hematological Malignancies

Conditions
Immunogenicity
Hematological Malignancies
Covid-19
Vaccine Response Impaired
Registration Number
NCT04878822
Lead Sponsor
Ospedale di Circolo - Fondazione Macchi
Brief Summary

Covid-19 is associated with a mortality rate of 33-37% in patients with hematological malignancies.

At present, the anti-SARS-CoV-2 vaccination represents the most effective strategy for the prevention of Covid-19. Patients with malignancies were excluded from the trials leading to the approval of Comirnaty, Moderna, Vaxzevria and Janssen vaccines. The immunogenicity of these vaccines in immunocompromised patients or with hematological malignancies is an unmet clinical need.

The aim of the study is to evaluate the efficacy of vaccination in adult patients with hematological malignancies, who received vaccination according to Italian rules and were in treatment at the Hematology Unit of Varese, Italy Efficacy will be evaluated in terms of serological response, cellular-mediated immune response and prevention of Covid-19.

The duration of the study will be 24 months.

Detailed Description

Covid-19 is associated with a mortality rate of 33-37% in patients with hematological malignancies (Passamonti et al, 2020; Garcia-Suarez et al, 2020). Currently, there is little information on the serological response following SARS-Cov-2 infection in this specific population.

At present, the anti-SARS-CoV-2 vaccination represents the most effective strategy for the prevention of Covid-19. The anti-SARS-CoV-2 vaccines currently approved by the European Medicines Agency (EMA) and the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA) are: the BNT162b2 SARS-Cov-2 (Pfizer-BioNTech, Comirnaty) vaccine, the mRNA-1273 SARS-Cov-2 (Moderna) vaccine, the ChAdOx1 nCoV-19 (Vaxzevria) vaccine, and the Ad26.COV2.S (Janssen) vaccine.

The double-dose regimen of Pfizer-BioNTech vaccine showed 95% efficacy at preventing Covid-19 (Polack et al, 2020), the double-dose regimen of Moderna vaccine showed 94.1% efficacy (Baden et al, 2021), the double-dose regimen of Vaxzevria vaccine showed 70.4% efficacy (Voysey et al, 2021), while the single-dose regimen of Janssen vaccine was found to be 66.1% effective (Sadoff et al, 2021).

The Italian national Covid-19 vaccination plan included patients with active malignancies in the second priority group, recognizing the importance of protecting this vulnerable population from SARS-Cov-2 infection. Since vaccine clinical trials excluded patients with malignancies and patients undergoing immunosuppressive therapies, the immunological response to anti-SARS-CoV-2 vaccines in these patients is currently unknown.

In this prospective, cohort, non-interventional study, our objective is to evaluate both the humoral and the cellular immune response to anti-SARS-CoV-2 vaccination in adults with hematological malignancies. For each patient the immune response will be evaluated after a minimum of 28 days from the completion of the vaccination regimen. Then, it will be reassessed after 6 and 12 months. In our center, the humoral immune response will be assessed by using the DiaSorin's LIAISON SARS-CoV-2 S1/S2 IgG test, which quantifies the level of anti-SARS-CoV-2 IgG antibodies that are active against the S1 and S2 subunits of the S protein. The cell-mediated immune response will be assessed on peripheral blood cells through a phenotypic and functional analysis by flow cytometry and through the ELISPOT test. Each patients will sign an informed consensus for the participation. The total duration of the study will be 24 months.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
300
Inclusion Criteria
  • Age ≥ 18 years.
  • History of hematological neoplasia (myeloid neoplasms, lymphoid neoplasms, plasma cell dyscrasias).
  • Active hematological neoplasm.
Exclusion Criteria
  • Hematological diseases, other than hematological malignancies.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
To evaluate the humoral immune response to SARS-CoV-2 / Covid-19 vaccination.1 month after completion of vaccination

The percentage of patients with positive antibody titer (≥ 12 AU / mL) after at least 28 days from vaccination.

Secondary Outcome Measures
NameTimeMethod
To evaluate the humoral immune response to SARS-CoV-2 / Covid-19 vaccination according to the disease and its status.1 month after completion of vaccination

The percentage of patients with positive antibody titer (≥ 12 AU / mL) after at least 28 days from vaccination in myeloid, lymphoid and plasma cell dyscrasias sub-categorized by status of disease, status and type of treatment.

To evaluate the cellular immune response to SARS-CoV-2 / Covid-19 vaccination.28 days, 6 and 12 months after completion of vaccination

The percentage of patients who generated immune cells with IFN-gamma cytokine response after at least 28 days, 6 and 12 months after vaccination.

To evaluate the humoral immune response to SARS-CoV-2 / Covid-19 vaccination according to the type of vaccination.1 month after completion of vaccination

The percentage of patients with positive antibody titer (≥ 12 AU / mL) after at least 28 days from vaccination described by vaccine brand (currently Comirnaty, Moderna, Vaxzevria, Janssen).

To evaluate the clinical efficacy of the anti SARS-CoV-2 / Covid-19 vaccination.28 days, 6 and 12 months after completion of vaccination

The percentage of patients with any among: 1) positive molecular swab by RT-PCR, 2) documented symptomatic Covid-19 disease; 3) hospitalization for Covid-19; 4) documented severe Covid-19 disease; 5) death from Covid-19 despite vaccination.

To evaluate the persistence of the antibody titer after vaccination.28 days, 6 and 12 months after completion of vaccination

The difference between the antibody titer at 28 days and at 6 and 12 months after vaccination.

To assess the antibody titer at least 28 days after the SARS-CoV-2 / Covid-19 vaccination.1 month after completion of vaccination

The distribution and median of the antibody titer at least 28 days after vaccination.

Trial Locations

Locations (1)

UOC Ematologia, ASST Sette Laghi, Osp. Di Circolo e Fondazione Macchi

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Varese, Lombardia, Italy

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