Determinants of Neutralizing Antibody Response After SARS CoV-2 Vaccination in Patients With Myeloma

• Type of Material: Article
• Authors: Ajay Nooka, Emory University; Uma Shanmugasundaram, Emory University; Narayanaiah Cheedarla, Emory University; Hans Verkerke, Emory University; Venkata V Edara, Emory University; Rajesh Valanparambil, Emory University; Jonathan Kaufman, Emory University; Nisha Joseph, Emory University; Craig Hofmeister, Emory University; Sagar Lonial, Emory University; Maryam Azeem, Emory University; Julia Manalo, Emory University; Jeffrey Switchenko, Emory University; Andres Chang, Emory University; Susanne L Linderman, Emory University; John Roback, Emory University; Kavita Dhodapkar, Emory University; Rafi Ahmed, Emory University; Mehul Suthar, Emory University; Andrew Neish, Emory University; Madhav Dhodapkar, Emory University
• Language: English
• Date: 2022-09-10
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Final Published Version
• Copyright Statement: © 2022 by American Society of Clinical Oncology
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.21.02257
• Title of Journal or Parent Work: JOURNAL OF CLINICAL ONCOLOGY
• Volume: 40
• Issue: 26
• Start Page: 3057
• End Page: +
• Grant/Funding Information: K.M.D. was supported in part by funds from NIH (CA238471 and AR077926).; M.S.S. was supported in part by grants (P51 OD011132, HHSN272201400004C, and U19AI090023) from National Institutes of Health (NIH), by the Emory Executive Vice President for Health Affairs Synergy Fund award, the Pediatric Research Alliance Center for Childhood Infections and Vaccines and Children's Healthcare of Atlanta, COVID-Catalyst-I3 Funds from the Woodruff Health Sciences Center and Emory School of Medicine, Woodruff Health Sciences Center 2020 COVID-19 CURE Award, and the Emory-UGA Center of Excellence for Influenza Research and Surveillance.; Supported in part by NCI U54CA260563. M.V.D. was also supported by funds from the NCI R35CA197603 and SCOR award from LLS
• Keywords: Oncology; Science & Technology; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Oncology; Health Sciences, Pathology

Abstract

PURPOSEVaccine-induced neutralizing antibodies (nAbs) play a critical role in protection from SARS CoV-2. Patients with B-cell malignancies including myeloma are at increased risk of COVID-19-related mortality and exhibit variable serologic response to the vaccine. The capacity of vaccine-induced antibodies in these patients to neutralize SARS CoV-2 or its variants is not known.METHODSSera from 238 patients with multiple myeloma (MM) undergoing SARS CoV-2 vaccination were analyzed. Antibodies against the SARS CoV-2 spike receptor-binding domain (RBD) and viral nucleocapsid were measured to detect serologic response to vaccine and environmental exposure to the virus. The capacity of antibodies to neutralize virus was quantified using pseudovirus neutralization assay and live virus neutralization against the initial SARS CoV-2 strain and the B1.617.2 (Delta) variant.RESULTSVaccine-induced nAbs are detectable at much lower rates (54%) than estimated in previous seroconversion studies in MM, which did not monitor viral neutralization. In 33% of patients, vaccine-induced antispike RBD antibodies lack detectable neutralizing capacity, including against the B1.617.2 variant. Induction of nAbs is affected by race, disease, and treatment-related factors. Patients receiving mRNA1273 vaccine (Moderna) achieved significantly greater induction of nAbs compared with those receiving BNT162b2 (Pfizer; 67% v 48%, P =.006).CONCLUSIONThese data show that vaccine-induced antibodies in several patients with MM lack detectable virus-neutralizing activity. Vaccine-mediated induction of nAbs is affected by race, disease, vaccine, and treatment characteristics. These data have several implications for the emerging application of booster vaccines in immunocompromised hosts.