Onishi Akio, Matsumura-Kimoto Yayoi, Mizutani Shinsuke, Tsukamoto Taku, Fujino Takahiro, Miyashita Akihiro, Nishiyama Daichi, Shimura Kazuho, Kaneko Hiroto, Kawata Eri, Takahashi Ryoichi, Kobayashi Tsutomu, Uchiyama Hitoji, Uoshima Nobuhiko, Nukui Yoko, Shimura Yuji, Inaba Tohru, Kuroda Junya
Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Hematology, Japan Community Health Care Organization Kyoto Kuramaguchi Medical Center, Kyoto, Japan.
Infect Drug Resist. 2023 Jan 25;16:509-519. doi: 10.2147/IDR.S396271. eCollection 2023.
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).
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.
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.
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.
抗CD20单克隆抗体（MoAbs），利妥昔单抗（RIT）和奥妥珠单抗（OBZ）是B细胞淋巴瘤（BCL）免疫化疗的核心组成部分。然而，这些药物可能导致B细胞耗竭，从而损害抗体（Ab）的产生。在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）大流行期间，对于接受B细胞耗竭疗法治疗的BCL患者，最佳预测抗SARS-CoV-2疫苗接种后的抗体反应对于预防2019冠状病毒病（COVID-19）至关重要。
我们调查了2021年6月至11月期间，在京都临床血液学研究组所属的7家机构中，131例接受含B细胞耗竭成分的免疫化疗后、期间或之前接种第二剂SARS-CoV-2 mRNA疫苗的各类BCL患者中，使用RIT和/或OBZ对抗体反应的影响。使用iFlash3000自动分析仪和iFlash-2019-nCoV Nab试剂盒，在接种第二剂疫苗后14至207天测量SARS-CoV-2中和抗体（nAb）。
在B细胞耗竭治疗后12个月内接种疫苗的86例患者中，8例（9.3%）血清学呈阳性。在B细胞耗竭治疗12个月后接种疫苗的30例患者中，22例（73%）血清学呈阳性。在接种疫苗后接受B细胞耗竭治疗的15例患者中，2例（13%）血清学呈阳性。多因素分析表明，B细胞耗竭治疗与随后接种疫苗之间间隔12个月与有效的抗体产生显著相关。受试者工作特征曲线分析确定，抗CD20 MoAb治疗后决定SARS-CoV-2血清学阳性的最佳阈值期为342天。
在接种疫苗前12个月内使用抗CD20 MoAb是BCL患者抗SARS-CoV-2疫苗接种抗体反应不佳的关键风险因素。
