Variations in preexisting antibody titers against viruses in patients with diffuse large B cell lymphoma undergoing frontline anti-CD20-containing chemotherapy Restricted; Files Only

Abstract

Patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia (NHL/CLL) are at higher risk of more frequent and severe infections as they have immune system defects that arise from the cancer itself and from the treatments they receive. Vaccines are a cornerstone of infection prevention, but patients with NHL/CLL elicit suboptimal antibody responses after vaccination. However, the effect of lymphoma diagnosis and treatment on the quantity and quality of preexisting antibodies has not been studied. We conducted a prospective cohort study to measure the changes in IgG antibody titers against the SARS-CoV-2 wild type spike protein (S WT), measles, and rubella in patients with a new diagnosis of an aggressive B cell lymphoma throughout their treatment period and up to 1 year after. A total of 33 patients with an aggressive B cell lymphoma and 9 healthy control individuals were enrolled. All patients in the lymphoma cohort received lymphoma-directed therapies that consisted of the anti-CD20 antibody rituximab and combination cytotoxic chemotherapy, per standard of care. At baseline, all patients with lymphoma and healthy controls had detectable levels of anti-S WT IgG but 35% of the lymphoma patients had titers over 5 times below the median titers observed in healthy controls. Seroprevalence did not change at the 1-year timepoint but median anti-S WT IgG titers declined significantly from 55,524 to 36,636 AU/mL (p=0.01). Median titers in healthy controls, remained constant over the course of 1 year. Using a mixed effect model, we estimated that it would take 192 days (95% CI of 157-247 days) for anti-S WT IgG titers in the plasma of lymphoma patients to reach half of their concentration vs 444 days (95% CI of 317-742 days) in healthy controls. No significant associations were observed between antibody decay rates and demographic, clinical, or treatment factors. Median anti-measles and anti-rubella IgG titers did not significantly change during the observation period. Thus, our study shows that lymphoma diagnosis and treatment have a differential effect on antibody decay rates, with antibodies maintained primarily by antibody-secreting B cells being affected while those maintained by long-lived plasma cells remaining largely preserved.

Table of Contents

Introduction 1

The normal antibody response after vaccination 2

Antibody responses after vaccination in NHL/CLL patients 4

Methods 6

Study design 6

Sample processing 7

SARS-CoV-2 Antibody binding assay 7

Measles and rubella-specific ELISA 8

Antibody titer modeling 9

Statistical analysis 9

Results 10

Kinetics of anti-SARS-CoV-2 binding IgG titers 11

Kinetics of anti-measles and anti-rubella binding IgG titers 13

Discussion 14

Study strengths 17

Study limitations 18

Future Directions 18

Conclusions 20

Tables and Figures 22

Figure 1. Antibody responses after SARS-CoV-2 vaccine in NHL/CLL. 22

Figure 2. Antibody responses after booster vaccination. 23

Figure 3. Study Schema. 24

Table 1. Clinical characteristics of the study population. 25

Table 2. Select baseline laboratory values for the study population. 26

Figure 4. Kinetics of anti-S WT IgG titers after induction therapy with rituximab and chemotherapy in patients with aggressive B cell lymphomas. 27

Table 3. Percent decline in anti-S WT IgG binding titers per month 28

Table 4. Percent decline in anti-measles and rubella IgG binding titers per year 30

References 31

About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Immunology Health Sciences, Medicine and Surgery
Keyword	vaccine antibody response chronic lymphocytic leukemia non Hodgkin lymphoma
Committee Chair / Thesis Advisor	Jordan Kempker, Emory University
Committee Members	Amita Manatunga, Emory University Rafi Ahmed, Emory University Jonathon Cohen, Emory University

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