Impact of Treatment with Anti-CD20 Monoclonal Antibody on the Production of Neutralizing Antibody Against Anti-SARS-CoV-2 Vaccination in Mature B-Cell Neoplasms

Akio Onishi; Yayoi Matsumura-Kimoto; Shinsuke Mizutani; Taku Tsukamoto; Takahiro Fujino; Akihiro Miyashita; Daichi Nishiyama; Kazuho Shimura; Hiroto Kaneko; Eri Kawata; Ryoichi Takahashi; Tsutomu Kobayashi; Hitoji Uchiyama; Nobuhiko Uoshima; Yoko Nukui; Yuji Shimura; Tohru Inaba; Junya Kuroda

doi:10.2147/IDR.S396271

Impact of Treatment with Anti-CD20 Monoclonal Antibody on the Production of Neutralizing Antibody Against Anti-SARS-CoV-2 Vaccination in Mature B-Cell Neoplasms

Infect Drug Resist. 2023 Jan 25:16:509-519. doi: 10.2147/IDR.S396271. eCollection 2023.

Authors

Akio Onishi¹, Yayoi Matsumura-Kimoto^{1

2}, Shinsuke Mizutani¹, Taku Tsukamoto¹, Takahiro Fujino¹, Akihiro Miyashita^{1

3}, Daichi Nishiyama⁴, Kazuho Shimura⁵, Hiroto Kaneko⁵, Eri Kawata⁶, Ryoichi Takahashi⁷, Tsutomu Kobayashi^{1

8}, Hitoji Uchiyama⁸, Nobuhiko Uoshima³, Yoko Nukui⁹, Yuji Shimura¹, Tohru Inaba⁹, Junya Kuroda¹

Affiliations

¹ Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
² Department of Hematology, Japan Community Health Care Organization Kyoto Kuramaguchi Medical Center, Kyoto, Japan.
³ Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
⁴ Department of Hematology, Fukuchiyama City Hospital, Fukuchiyama, Japan.
⁵ Department of Hematology, Aiseikai Yamashina Hospital, Kyoto, Japan.
⁶ Department of Hematology, Matsushita Memorial Hospital, Moriguchi, Japan.
⁷ Department of Hematology, Omihachiman Community Medical Center, Omihachiman, Japan.
⁸ Department of Hematology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.
⁹ Division of Infection Control & Molecular Laboratory Medicine, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Abstract

Background and purpose: Anti-CD20 monoclonal antibodies (MoAbs), rituximab (RIT), and obinutuzumab (OBZ) are the central components of immunochemotherapy for B-cell lymphoma (BCL). However, these agents potentially cause B-cell depletion, resulting in the impairment of antibody (Ab) production. During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the optimal prediction of Ab response against anti-SARS-CoV-2 vaccination is critically important in patients with BCL treated by B-cell depletion therapeutics to prevent coronavirus disease 2019 (COVID-19).

Patients and methods: We investigated the effect of using RIT and/or OBZ on the Ab response in 131 patients with various types of BCL who received the second SARS-CoV-2 mRNA vaccine either after, during, or before immunochemotherapy containing B-cell-depleting moiety between June and November 2021 at seven institutes belonging to the Kyoto Clinical Hematology Study Group. The SARS-Cov-2 neutralizing Ab (nAb) was measured from 14 to 207 days after the second vaccination dose using the iFlash3000 automatic analyzer and the iFlash-2019-nCoV Nab kit.

Results: Among 86 patients who received the vaccine within 12 months after B-cell depletion therapy, 8 (9.3%) were seropositive. In 30 patients who received the vaccine after 12 months from B-cell depletion therapy, 22 (73%) were seropositive. In 15 patients who were subjected to B-cell depletion therapy after vaccination, 2 (13%) were seropositive. The multivariate analysis indicated that an interval of 12 months between B-cell depletion therapy and the subsequent vaccination was significantly associated with effective Ab production. Receiver operating characteristic curve analysis identified the optimal threshold period after anti-CD20 MoAb treatment, which determines the seropositivity against SARS-CoV-2, to be 342 days.

Conclusion: The use of anti-CD20 MoAb within 12 months before vaccination is a critical risk for poor Ab response against anti-SARS-CoV-2 vaccination in patients with BCL.

Keywords: B-cell lymphoma; COVID-19; anti-CD20 monoclonal antibody; vaccine.

Grants and funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.