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POS1202 (2022)
B-CELL RECONSTITUTION IS STRONGLY ASSOCIATED WITH A POSITIVE SEROLOGIC RESPONSE TO THE COVID-19 BOOSTER VACCINE IN PREVIOUSLY SEROLOGICALLY UNRESPONSIVE RITUXIMAB TREATED RHEUMATIC DISEASE PATIENTS
K. Schultz1, D. Jannat-Khah1,2, R. Spiera1,2
1Hospital for Special Surgery, Medicine, New York, United States of America
2Weill Cornell Medical College, Medicine, New York, United States of America

Background: Booster doses of SARS-CoV-2 vaccines have emerged as an important strategy for containing the pandemic and may be especially important to rituximab treated patients. B-cell depletion has been associated with worse outcomes from COVID-19 infection, and many rituximab treated patients demonstrate an inadequate serologic response to the initial vaccine series (1). Strategies to optimize serologic response to COVID-19 vaccine boosters in previously serologically unresponsive patients is, therefore, of particular relevance.


Objectives: To assess factors associated with serologic response to COVID-19 booster vaccines in rituximab treated patients previously serologically unresponsive to the initial vaccine series.


Methods: A retrospective chart review of rituximab treated patients who failed to demonstrate a serologic response to the first SARS-CoV-2 vaccination series and subsequently received an mRNA vaccine booster was performed. Serologic response four weeks or more after the booster was the primary outcome. T-tests, Fisher’s exact tests, and Wilcoxon rank sum tests were used for comparisons. Box and whisker plots were constructed to visualize differences between serologic response.


Results: In 31 rituximab treated patients who were seronegative following the initial vaccine series, demographic characteristics, concurrent therapies, rheumatologic diagnosis, and vaccine type were not associated with serologic positivity to the booster vaccine ( Table 1 ). B-cell reconstitution was significantly different between those with positive (median, IQR 1.785 (0.65, 3)) and negative (median, IQR 0 (0,0)) serologic responses to the booster (p-value<0.001) as was time from last rituximab exposure (p-value = 0.030) ( Figure 1 ). Positive predictive value of B-cell presence was 90.9% (95% CI: 70.8%, 98.9%) and negative predictive value was 100% (95% CI: 59%, 100%) for serologic response to the mRNA booster. Positive predictive value of time >6 months from last rituximab to the booster was 78.3% (95% CI 56.3%, 92.5%) and the negative predictive value was 62.5% (95% CI 24.5%, 91.5%).

Bivariate comparisons between seronegative and seropositive patients to the COVID-19 booster vaccine by patient characteristics and demographics

Factor Value Negative Positive p-value a
N 31 10 21
Age, median (IQR ) 64 (51, 72) 63 (51, 69) 65 (51, 73) 0.75
Sex 1.00
 Female 23 (74%) 7 (70%) 16 (76%)
 Male 8 (26%) 3 (30%) 5 (24%)
Any immunosuppressant b 9 (29%) 3 (30%) 6 (29%) 1.00
Corticosteroid 5 (16%) 1 (10%) 4 (19%) 1.00
3 rd Vaccine dose type 0.24
 Pfizer 19 (61%) 8 (80%) 11 (52%)
 Moderna 12 (39%) 2 (20%) 10 (48%)
Dichotomous B-cell status around booster dose <0.001
 No detectable B-cells 7 (23%) 7 (70%) 0 (0%)
 Detectable B-cells 22 (71%) 2 (20%) 20 (95%)
 Missing 2 (6%) 1 (10%) 1 (5%)
Time from last RTX infusion to booster, median (IQR ) 260 (216, 379) 188 (169, 245) 301 (251, 368) 0.030
Time from last RTX infusion to booster dose 0.10
 <6months 8 (25.81%) 5 (50%) 3 (14%)
 6-12 months 15 (48.39%) 3 (30%) 12 (57%)
 >12 months 8 (25.81%) 2 (20%) 6 (29%)

a P-values are from Fisher’s exact test, Student’s T-test and Wilcoxon rank sum tests

b Immunosuppressants included Leflunomide, Azathioprine, Methotrexate, Mycophenolate Mofetil, and Tocilizumab

IQR= Interquartile range


Conclusion: Presence of detectable B-cells and longer time from last rituximab were associated with the development of SARS-CoV-2 spike protein antibodies following the booster vaccine. These factors should be considered in timing of administration of booster vaccine doses in previously unresponsive rituximab treated patients.


REFERENCES:

[1]Levavi H, Lancman G, Gabriolove J. Impact of rituximab on COVID-19 outcomes. Ann Hematol 2021;100:2805-12.


Disclosure of Interests: Kaitlin Schultz: None declared, Deanna Jannat-Khah Shareholder of: Cytodyn, Astrazeneca, Walgreens, Robert Spiera Consultant of: AbbVie, Regeneron, Sanofi, Chemomab, Formation Biologics, GSK, Janssen Pharmaceuticals, Chemocentryx, Grant/research support from: GSK, Boehringer Ingelheim Pharmaceuticals, Corbus Pharmaceuticals, Formation Biologics, InflaRx, Kadmon, Astrazeneca, AbbVie, Sanofi, Genentech/Roche, Principia, Novartis


Citation: , volume 81, supplement 1, year 2022, page 929
Session: COVID-19 (POSTERS only)