Those undergoing treatment for hematological malignancies show reduced immune response to COVID-19 vaccines

It has been well established that the coronavirus disease 2019 (COVID-19) disproportionately affects certain ethnic groups, such as individuals of African or Caribbean descent. COVID-19 has also been associated with a higher risk of both sickness and death in those suffering from hematological malignancies such as non-Hodgkins lymphoma. However, few studies have examined the interactions between these two factors.

Study: High Seroconversion Rates Amongst Black and Hispanics With Hematologic Malignancies after SARS-CoV-2 Vaccination. Image Credit: Frame Stock Footage / Shutterstock.com

To this end, researchers from the Albert Einstein College of Medicine have recently investigated the effect of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with hematologic malignancies in minority populations.

Background

Due to safety concerns, patients with cancer were not involved in any vaccine trials for the Pfizer, Moderna, or Johnson & Johnson vaccines. While these vaccines have been shown to be safe and effective for the general population, this may not be true for subgroups of cancer patients with certain hematologic malignancies, including chronic lymphocytic leukemia (CLL), multiple myeloma, and patients treated with B-cell depleting therapies.

Although immunocompromised individuals will likely be protected by herd immunity eventually, concerns have emerged for their short short-term safety following the release of evidence suggesting lower rates of seroconversion for the SARS-CoV-2 immunoglobulin G (IgG) anti-spike antibodies, which could lead to lower protection against COVID-19.

The spike (S) protein is potentially the most important protein of SARS-CoV-2. The S protein consists of an S1 subunit, which contains the receptor receptor-binding domain (RBD) that binds to the angiotensin-converting enzyme 2 (ACE2) receptor of the host cell. This interaction between the RBD of SARS-CoV-2 and the ACE2 receptor allows viral entry into the cell, whereas the N-terminal domain enables membrane fusion.

About the study

The researchers of the current study examined the seroconversion rates of 116 patients in total, testing for anti-spike IgGs using a commercially available immunoassay. Ten of these patients were not included in the final analysis due to S protein IgG testing occurring before the second dose of the vaccine was administered.

The participants were examined using standard descriptive statistics, with the associations between their characteristics, cancer types, treatments, and response to the vaccine being assessed using the Fisher Exact or Kruskal-Wallis Rank Sum tests.

In total, 74% of patients were minorities. Additionally, 60% of all participants received the Pfizer vaccine, whereas 31% and 9% received the Moderna and Johnson & Johnson vaccines, respectively.

A high rate of 86% seropositivity was observed in the current study, whereas 14% of patients showed no anti-spike IgG. Of the 86 minority patients included in the current study, 94% of Blacks and 87% of Hispanics were found to have seropositivity with a median level of 2,157 AU/ml.

Patients with lymphoid malignancies showed a significantly lower seroconversion rate of 70% lower as compared to the median. Individuals who received cytotoxic chemotherapy or other B cell depleting therapies such as monoclonal antibody treatment also exhibited significantly lower seroconversion rates.

Patients with myeloid and plasma cell neoplasms were not as badly affected, with 96% and 98%, respectively, exhibiting seropositivity. Unsurprisingly, patients who had previously recovered from COVID-19 showed significantly higher antibody titers, a finding which is supported by multiple previous studies in healthy individuals. Luckily, no severe side effects to the vaccines were reported in immunocompromised individuals, with the most common side effect including muscle aches, fatigue, and fever.

Study takeaways

The new vaccine designs, including the messenger ribonucleic acid (mRNA) vaccines and nanoparticle nanoparticle-based vaccines, should allow for greater effectivity without any increased risk for cancer sufferers.

The authors also highlight how their study supports previously published literature in showing that those on immunosuppressant treatments are at greater risk of the virus, while also suffering less protection from the vaccine. Notably, the results of the current study also identify the increased risk of patients undergoing cytotoxic chemotherapy.

Taken together, the researchers recommend vaccination for all patients receiving chimeric antigen receptor T-cell (CART) therapy before chemotherapy begins. One of the more surprising results was the outcome of patients with myeloid malignancies and plasma cell neoplasms, which showed promising immune activity following vaccination despite patient history, with the two most common treatments actually showing higher seroconversion rates.

Another new finding is the interactions across ethnicity and hematological malignancy, with non-white patients showing both increased risk of morbidity and mortality. This makes the scientists' goal of overcoming vaccine hesitancy even more important, as increased rates of COVID-19 have been reported in non-white individuals as compared to white individuals.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information

Journal reference:
Sam Hancock

Written by

Sam Hancock

Sam completed his MSci in Genetics at the University of Nottingham in 2019, fuelled initially by an interest in genetic ageing. As part of his degree, he also investigated the role of rnh genes in originless replication in archaea.

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