Differential Antiviral IgG Titer Decay Rates after Frontline Chemoimmunotherapy in Patients with Aggressive B Cell Lymphoma

• Published in: Blood 2024-11, Vol.144, p.6242-6242
• Main Authors: Chang, Andres, Leal, Alyssa, Churnetski, Michael, Lai, Lilin, Linderman, Susanne, Ahmed, Hasan, O'Leary, Colin B, Antia, Rustom, Dhodapkar, Madhav V., Suthar, Mehul, Koff, Jean L., Cohen, Jonathon B, Ahmed, Rafi
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-200324

Introduction Patients with B cell malignancies remain at high risk of morbidity and mortality from respiratory viruses like SARS-CoV-2. These patients often receive B cell-depleting agents in combination with chemotherapy as part of their cancer treatment, impairing their subsequent capacity to generate antibody responses to infection and vaccination. However, less is known about the effects of these aggressive treatments on already acquired humoral immunity in this population. Objective To determine the effect of frontline chemoimmunotherapy with anti-CD20 antibodies on established antibody titers against SARS-CoV-2, measles, and rubella over time in patients with newly diagnosed aggressive B cell non-Hodgkin lymphoma (aNHL). Methods Patients with a new diagnosis of aNHL were enrolled after informed consent. Serial blood samples were obtained before, during, and up to 1 year after treatment with regimens containing an anti-CD20 antibody + multiagent chemotherapy. IgG binding titers against the SARS-CoV-2 nucleocapsid (N) protein and the spike protein of several SARS-CoV-2 variants were measured with a multiplex assay. Live virus neutralization titers against SARS-CoV-2 variants over time were also measured. IgG titers against measles and rubella were measured by ELISA. Antibody decay half-lives were calculated using exponential model. Clinical information was abstracted from the electronic medical record and correlated with antibody responses. Results A total of 42 individuals were enrolled (33 with aNHL, 9 healthy donor controls). For the aNHL group, mean age was 59.7, 51.5% were male, and 39.4% non-white. Mean number of vaccine doses was 3 with a mean of 199 days between last vaccine and cycle 1 of lymphoma-directed therapy. All patients received rituximab as their anti-CD20 antibody and only 2 patients did not receive an anthracycline. Before treatment (baseline), 56.5% of aNHL patients did not show anti-N antibodies to indicate prior infection. Greater variability in IgG binding titers against wild-type (WT) spike protein and significantly lower neutralization titers were observed in aNHL at baseline vs controls (mean titer 1227 vs 1822 AU/mL, p