A third leading SARS-CoV-2 mRNA vaccine enhances antibody responses in most patients with hematologic malignancies

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and the resulting disease, COVID-19, first appeared in 2019, before being declared a pandemic by WHO in March 2020. Did.Elderly people, people with chronic diseases such as cancer^1,2,3Hematologic cancer patients were defined as highly clinically vulnerable to COVID-19 and advised to protect themselves during the first and subsequent waves of infection. In the first wave, patients with hematologic malignancies (HM) had poor outcomes, with mortality rates of 20-40%.^{Four,Five,6,7}.

UK data during the first Omicron wave (December 2021 to April 2022) show proportionately fewer hospitalizations and deaths than in previous waves, despite high levels of community transmission. increase. This change may be multifactorial. It is driven primarily by the characteristics of virus variants, the population-level immune protection conferred by vaccination, and the availability of antiviral and monoclonal antibody therapy, especially in non-hospitalized settings.

Prophylactic vaccines focus on immunization with the spike (S) protein, the primary target of neutralizing antibodies.Neutralizing antibodies block viral entry into host cells by preventing interaction between the spike protein receptor-binding motif and the host cell’s angiotensin-converting enzyme-2, and vaccines are expected to protect alpha strains. was being^8,9Although commercial quantitative anti-S antibody assays are widely available, uncertainty remains as to what threshold anti-S IgG titers correlate with effective virus neutralization. found a high mortality rate among patients hospitalized with COVID-19 who had no detectable antibody response on admission, and found that treatment with casilibimab and imedevimab, a neutralizing monoclonal antibody (nMAB) cocktail, reduced the relative risk of death from infection. 20% during premicron waves^TenIn the immunocompromised group, NHS-England has expanded the use of casilibimab and imedevimab to people with very low antibody responses, defined as anti-S titers in the bottom 10% of the detection range of the assay.¹¹Later, the emergence of Omicron strains resistant to casilibimab and imedevimab limited its use to those infected with the delta variant.¹²However, other omicron-active nMABs have shown efficacy in reducing hospitalization and mortality when provided in the community early in the disease course.¹³and new data support the prophylactic use of nMABs with extended half-lives in people with inadequate vaccine responses¹⁴.

The extent to which vaccination protects patients with hematologic cancers is unclear and likely heterogeneous. seems to show¹⁵However, the OCTAVE study reported the first 600 patients, including those with haematological malignancies and stem cell transplants (n= 80), 4 weeks after the second primary vaccination, 11.1% and 11.9%, respectively, reported no measurable anti-spike antibody response.¹⁶While data about responses to subsequent vaccines began to emerge^17,18the granularity of heterogeneity in this patient group remains unclear.

Patients with hematological cancers are one of the highest priority groups to receive SARS-CoV-2 vaccination in the UK, with most patients undergoing mRNA-based Pfizer-BioNTech-BNT162b2 or adenovirus-based AstraZeneca-ChAdOx1 – have received any of S/nCoV-19. Both require two doses of vaccination to complete the primary course, and in the UK the second primary vaccination has been postponed to a 12-week interval for many people as an emergency public health measure. Based on early evidence of suboptimal antibody responses to the two vaccines in some patients, MHRA was recommended as a booster dose of a third primary mRNA dose, administered at least 8 weeks after completion of the second primary vaccination. Approved for use in base vaccines. An additional booster dose was made available 8 weeks after completion of the primary course.

Offer antiviral or nMAB to at-risk individuals, including those with hematological malignancies, at a central hub, reflecting emerging real-world data on suboptimal vaccine responses and continued vulnerability of high-risk groups A national outpatient treatment program was established in the UK for Currently, the program prioritizes oral antivirals over nMAB and does not differentiate treatment preferences based on vaccine status or serological response.

Here, we report actual vaccine-induced SARS-CoV-2 antibody responses in patients with hematologic malignancies from the MARCH (Monitoring Adaptive Responses to COVID-19 Vaccines in Hematology) study. This is a retrospective observational study with data drawn from the MARCH research database. The purpose of the MARCH study is to use real-world data to determine the adaptive immune response of a patient with a hematologic disease to her COVID-19 vaccination. The study database included patients 18 years of age or older who had a history of hematologic disease (including lymphoma), who were undergoing clinical care at our institution, and who had at least one of his I am undergoing a SARS-CoV2 antibody test. In this study, we report the serological response to SARS-CoV2 vaccination in SARS-CoV2-naive individuals with hematologic malignancies.¹⁵.