Abstract 5277: Humoral SARS-CoV-2 response in asymptomatic precursor plasma cell dyscrasia patients: IMPACT study results
Authors: Konishi Yoshinobu , Sklavenitis-Pistofidis Romanos , Yue Hong , Ferrari Federico , Russo Massimiliano , Redd Robert A. , Perry Jacqueline , Horowitz Erica , Justis Anna V. , Shayegh Nader A. , Lightbody Elizabeth D. , Varmeh Shohreh , Nowak Radoslaw P. , Hamilton Mark , Auclair Daniel , Marinac Catherine R. , Trippa Lorenzo , Fischer Eric S. , Ghobrial Irene M. 
Published: June 2022

Abstract
Introduction: Patients with hematologic malignancies, including multiple myeloma (MM), experience worse SARS-CoV-2 infection outcomes and sub-optimal vaccine responses. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) precede MM and affect ~5% of individuals age &gt;=50. We previously showed that individuals with MGUS and SMM exhibit immune dysregulation. Here, we investigate the immune response to SARS-CoV-2 vaccination in these asymptomatic but potentially immunocompromised individuals.
Methods: The IMPACT study (IRB #20-332) is a prospective study at Dana-Farber Cancer Institute in collaboration with MMRF, which enrolled individuals nationwide with a diagnosed plasma cell dyscrasia and healthy individuals. As of October 2021, 3,005 individuals completed a questionnaire regarding prior infection or vaccination. We obtained 1,350 blood samples from 628 participants and analyzed anti-SARS-CoV-2 IgG antibody titer by ELISA.
Results: 2,771 (92%) participants were fully vaccinated (2 doses BNT162b2 or mRNA-1273; 1 dose Ad26.COV2.s), 269 (9%) had received a 3rd mRNA vaccine dose, and 234 (8%) were unvaccinated. 1,387 (46%) and 1,093 (36%) participants received mRNA vaccines (BNT162b2 and mRNA-1273), and 139 (5%) participants received an adenovirus vector vaccine (Ad26.COV2.S). 34 (1%) individuals reported SARS-CoV-2 infection after full vaccination.
We measured antibody titers in 201 MGUS, 223 SMM, 40 smoldering Waldenstrom macroglobulinemia (SWM), 64 MM, and 100 healthy controls. Multiple linear regression model estimated the association between various clinical variables and post-vaccination antibody titers. As previously reported, having MM was associated with low antibody titer (p &lt; 0.001). Of note, having SMM, regardless of risk stratification by 2/20/20 criteria, was also associated with low antibody titers, indicating that even low-risk SMM patients have a poor response to vaccination. MGUS and SWM diagnoses were not significantly associated with antibody titers. Additionally, male sex (p &lt; 0.010), elapsed time after vaccination (p &lt; 0.001), and BNT162b2 vaccine (p &lt; 0.001) were associated with low antibody titers. SARS-CoV-2 infection prior to vaccination was associated with high antibody titers.
We identified 25 patients (6 MGUS, 10 SMM, 2 SWM, 7 MM) who submitted blood samples after both the 2nd and 3rd dose. In these patients we observed a significant increase in antibody titer after a 3rd dose (p = 0.002). We also observed that antibody titers of patients after a 3rd dose (13 MGUS, 12 SMM, 2 SWM, 31 MM) were comparable to that of healthy individuals after a 2nd dose (p = 0.833).
Conclusion: Our data indicates that suboptimal response to SARS-CoV-2 does not only occur with MM and cancer patients receiving therapy but also in precursor asymptomatic patients including low-risk SMM.
Citation Format: Yoshinobu Konishi, Romanos Sklavenitis-Pistofidis, Hong Yue, Federico Ferrari, Massimiliano Russo, Robert A. Redd, Jacqueline Perry, Erica Horowitz, Anna V. Justis, Nader A. Shayegh, Elizabeth D. Lightbody, Shohreh Varmeh, Radoslaw P. Nowak, Mark Hamilton, Daniel Auclair, Catherine R. Marinac, Lorenzo Trippa, Eric S. Fischer, Irene M. Ghobrial. Humoral SARS-CoV-2 response in asymptomatic precursor plasma cell dyscrasia patients: IMPACT study results [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5277.