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Third Dose of COVID-19 Vaccine Significantly Increases Immune Responses in Most Patients With Multiple Myeloma


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Most immunocompromised people with multiple myeloma benefited from a third dose of COVID-19 vaccines—a promising sign after it was shown that two doses tended to not be sufficient for them. However, some people with multiple myeloma still remained vulnerable and may need a fourth dose or antibody treatments as restrictions lift and new variants emerge, according to a fast-tracked study published by Aleman et al in Cancer Cell.

“This study is the first to comprehensively capture the immune effect of the third dose of the COVID-19 vaccine in patients with plasma cell disorders and blood cancers like multiple myeloma,” said one of the study’s lead authors, Samir Parekh, MD, Director of Translational Research in Multiple Myeloma at The Tisch Cancer Institute at Mount Sinai, and Professor of Medicine (Hematology and Medical Oncology) and Oncological Sciences at the Icahn School of Medicine at Mount Sinai. “It provides guidance to patients [with myeloma], who are at risk for severe infection because they may be immunocompromised due to the disease itself and the cancer treatment.”

Samir Parekh, MD

Samir Parekh, MD

Mount Sinai’s previous research had shown that breakthrough infections occurred in patients with multiple myeloma due to poor or no response to the normal regimen of COVID-19 vaccines, the majority of which were the two-dose mRNA vaccines. These vulnerable patients’ lack of complete protection led to antibody testing and a third vaccine in hopes that this would increase the immune response. This study was important in understanding whether vulnerable patients were adequately protected by the third dose, or needed to continue to follow strict social distancing and masking or seek additional vaccines or treatments when available. 

Evidence of Activity of Third Dose

In this latest study, blood samples were collected from 476 patients with plasma cell disorders over a period of 15 months and were compared to samples collected from healthy, vaccinated health-care workers. The findings showed that the third dose significantly increased the level of antibodies in patients with and without prior COVID-19 infection, but levels of COVID-19–fighting antibodies in patients with multiple myeloma remained below those observed in healthy people.

Just more than a quarter of the patients with multiple myeloma had no detectable antibodies after the standard two doses of the vaccine, but in these patients, 88% developed antibodies after a third dose. The third dose also resulted in a significant increase of other immune cells such as T cells and B cells, which also help neutralize COVID-19.

After the third dose, neutralization of the wild-type virus increased in patients with multiple myeloma who had minimal or no response to the standard two doses. However, neutralizing titers against the Omicron variant were still lower in patients with multiple myeloma as compared to healthy controls. Therefore, a subset of patients may still remain vulnerable to SARS–CoV-2 infection.

“Our findings underscore the need for continued monitoring of immune responses and further research around measures such as additional vaccine doses or passive immunization for individual patients with multiple myeloma who may remain vulnerable after third-dose vaccination, especially as COVID-19 restrictions are being lifted worldwide and new waves of viral variants are emerging,” said the study’s other lead author, Viviana A. Simon, MD, PhD, Professor of Microbiology, Infectious Diseases, and Pathology, Molecular and Cell Based Medicine at the Icahn School of Medicine at Mount Sinai.

Disclosure: For full disclosures of the study authors, visit cell.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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