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. 2022 Jan 6;139(1):142-147.
doi: 10.1182/blood.2021013445.

Humoral and cellular responses after COVID-19 vaccination in anti-CD20-treated lymphoma patients

Nora Liebers  1   2 , Claudius Speer  3 , Louise Benning  3 , Peter-Martin Bruch  1 , Isabelle Kraemer  1 , Julia Meissner  1 , Paul Schnitzler  4 , Hans-Georg Kräusslich  4 , Peter Dreger  1 , Carsten Mueller-Tidow  1   2 , Isabel Poschke  5 , Sascha Dietrich  1   2   6
Affiliations

Humoral and cellular responses after COVID-19 vaccination in anti-CD20-treated lymphoma patients

Nora Liebers et al. Blood. .
No abstract available

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Figures

Figure 1
Figure 1
Humoral responses after COVID-19 vaccination in anti-CD20-treated lymphoma patients. (A) Seroconversion rates after the first and second COVID-19 vaccination (post V1: n = 57, post V2: n = 76). The median time from the first and second vaccination to serology testing was 15 days (IQR: 14–17 days) and 16 days (IQR: 14–24.2 days), respectively. The anti-SARS-Cov-2-S1 antibody response rate after the second vaccination was significantly higher than after the first vaccination (V2 vs V1: 41% [31/76] vs 9% [5/57], McNemar test P < .001). A semiquantitative index of <1 was classified as negative, and a value of ≥1 was classified as positive. All patients with an available sample prior to vaccination (n = 70, median sample collection prior to first vaccination: 254 days, IQR: 17–448 days) were tested negatively for anti-SARS-CoV-2-S1 and anti-SARS-CoV-2-N antibodies. (B) Seroconversion rates after the first and second COVID-19 vaccination according to the interval between the last anti-CD20 treatment and first COVID-19 vaccination (<3 months: post V1: n = 17, post V2: n = 19; >3 months and <12 months: post V1: n = 19, post V2: n = 23; >12 months: post V1: n = 21, post V2: n = 34). The seroconversion rate after the second vaccination was significantly increased when the interval between the last anti-CD20 treatment and first vaccination was >12 months compared with an interval of 3 months to 12 months (68% vs 22%, Fisher's exact test P = .001) or <3 months (68% vs 16%, Fisher's exact test P < .001). (C) Multivariate logistic regression analysis for seroconversion after the second vaccination in anti-CD20-treated patients (complete case analysis, n = 50). Independent predictors for seroconversion were age (per 10 years, OR 0.5 [95% CI 0.2–0.8], P = .008), the interval between last anti-CD20 treatment and first vaccination (per year, OR 2.2 [95% CI 1.3–4.7], P = .02), and the CD4 T-cell count (per 100 cells/µL, OR 1.6 [95% CI 1.2–2.3], P = .005). (D) SARS-CoV-2 neutralizing capacity of anti-CD20-treated lymphoma patients according to the anti-S1-measured seroconversion. The neutralizing capacity of COVID-19 vaccine-induced antibodies was measured with a SARS-CoV-2 surrogate virus-neutralizing assay. Values were normalized to a negative control, and the inhibition capacity of the SARS-CoV-2 receptor binding domain: angiotensin-converting enzyme 2 interaction was expressed as a percentage. A cutoff of 30% inhibition was applied according to the manufacturer's instructions and indicates the absence of a level of neutralizing antibodies below the limit of detection (represented by the dashed black line). The neutralizing antibody capacity was assessed in a subset of patients for whom additional samples were available (n = 38). Thirteen out of 15 patients (87%) with a positive anti-S1 antibody response had an inhibition exceeding the clinical cutoff for viral neutralization of 30%, whereas 22 out of 23 patients (96%) without seroconversion failed to achieve a successful neutralizing capacity. (E) SARS-CoV-2 neutralizing capacity of anti-CD20-treated lymphoma patients according to the interval between the last anti-CD20 treatment and first COVID-19 vaccination. The median neutralizing capacity after the second vaccination was significantly increased when the interval between the last anti-CD20 treatment and first vaccination was >12 months compared with an interval of 3 months to 12 months (12 months vs 3 months to 12 months: 86% [range 6% to 98%] vs 11% [range 4% to 23%], P = .002) or <3 months (12 months vs <3 months: 86% [range 6% to 98%] vs 21% [range 11% to 37%], P = .009). V1, vaccination 1; V2, vaccination 2; ns, not significant.
Figure 2
Figure 2
T-cell responses after COVID-19 vaccination in anti-CD20-treated lymphoma patients. (A) T-cell response rates in vaccinated patients (n = 50) and vaccinated healthy controls (n = 7) both after V2. A response was considered positive if mean spot-forming units (SFU) in peptide stimulated wells was >3 SFU above background, defined as mean SFU + 2 standard deviations of dimethylsulfoxide (DMSO)-exposed wells. Staphylococcal Enterotoxin B (SEB) served as the positive control. The median time between second vaccination and sample collection was 17 days (IQR 14–21 days) in the vaccinated patient cohort and 18 days (IQR 14–80 days) in the healthy control cohort. The T-cell response rate in the vaccinated healthy cohort was 71% (5/7) and 58% in the patient cohort with previous or ongoing anti-CD20 treatment (29/50). In patients and healthy controls with an available sample prior to vaccination, we observed positive T-cell responses (6 out of 26 patients, 1 out of 9 healthy controls, data not shown). These positive T-cell responses without prior COVID-19 infection were interpreted as a crossreactive response of memory T cells after prior infection with common cold coronaviruses. (B) T-cell response rates according to the anti-S1 seroconversion after the second vaccination. The T-cell response rate of patients with a successful seroconversion was 70% (14/20). Patients without a seroconversion still showed a T-cell response in 50% (15/30). The difference in T-cell response rates between patients with and without a seroconversion was not statistically significant (Fisher's exact test P = .2). (C) T-cell response rates after second vaccination according to the interval of last anti-CD20 treatment and first COVID-19 vaccination (<3 months: n = 15, >3 months and <12 months: post n = 12; >12 months: n = 23). The T-cell response rate was 57% (13/23), 67% (8/12), and 53% (8/15) when the last anti-CD20 treatment was administered >12 months, within >3 and <12 months, or <3 months prior to vaccination, respectively. No significant difference of the T-cell response between all 3 groups was observed (Fisher's exact test: >12 months vs >3 months and <12 months, P = .7; >12 months vs <3 months, P = 1.0; >3 months and <12 months vs <3 months, P = .7). (D) T-cell responses in patients with a proven negative prevaccination T-cell status. For 26 patients, prevaccination samples (median time of sample collection: 218.5 days [IQR 4.5–309 days]) prior to vaccination were available and tested for T-cell response. Out of the 26 patients, 20 patients had a negative T-cell response prior to vaccination. Representative ELISpot images were shown for a patient with diffuse large B-cell lymphoma who was treated with rituximab-CHOP and received the last cycle 48 days prior to the first vaccination. This patient had no SARS-CoV-2-S1 antibody response after 2 vaccinations with BNT162b2 (BioNTech). The left ELISpot panel shows the negative T-cell response measured in the sample 1 day prior to vaccination. The right ELISpot panel shows a positive T-cell response after 2 COVID-19 vaccinations (sample collection: 14 days post-second vaccination). The right bar plot shows the T-cell response rate after V2 in patients with a confirmed negative T-cell response prior to vaccination (n = 20). A positive T-cell response after vaccination was observed in 50% of patients (10/20). V1, vaccination 1; V2, vaccination 2; ns, not significant.
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