Poor Neutralizing Antibody Responses in 132 Patients with CLL, NHL and HL after Vaccination against SARS-CoV-2: A Prospective Study

Abstract

Emerging data suggest suboptimal antibody responses to COVID-19 vaccination in patients with hematological malignancies. We evaluated the humoral response following the BNT162b2 vaccine in patients with chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), and Hodgkin’s lymphoma (HL). An FDA-approved, ELISA-based methodology was implemented to evaluate the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 on day 1 of the first vaccine, and afterwards on day 22 and 50. One hundred and thirty-two patients with CLL/lymphomas and 214 healthy matched controls vaccinated during the same period, at the same center were enrolled in the study (NCT04743388). Vaccination with two doses of the BNT162b2 vaccine led to lower production of NAbs against SARS-CoV-2 in patients with CLL/lymphomas compared with controls both on day 22 and on day 50 (p < 0.001 for all comparisons). Disease-related immune dysregulation and therapy-related immunosuppression are involved in the low humoral response. Importantly, active treatment with Rituximab, Bruton’s tyrosine kinase inhibitors, or chemotherapy was an independent prognostic factor for suboptimal antibody response. Patients with HL showed superior humoral responses to the NHL/CLL subgroups. In conclusion, patients with CLL/lymphomas have low humoral response following COVID-19 vaccination, underlining the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures.

B-cell cytopenia and time to last B-cell-depleting therapy predict response to SARS-COV-2 vaccines in patients with lymphoproliferative disorders

“…In accordance with previous studies, our NHL patients generate poor antibody responses upon COVID vaccine administration, with a more pronounced deficiency detected after exposure to rituximab [18] , [19] , [20] , [21] , [22] . Our data demonstrates that poor seroconversion rates occur concomitantly with severe B-cell cytopenia, which is most severe within the first year post rituximab.…”

Reasons and consequences of COVID‐19 vaccine failure in patients with chronic lymphocytic leukemia

“…Patients with CLL under active surveillance or without active treatment produced antibodies followed the COVID‐19 vaccine more than people on treatment. 34 , 35 , 38 , 40 , 41 , 60 , 64 The number of prior treatment lines did not influence the seropositivity rate. The antibody response rate in patients receiving BTKi was 16.0% and 13.6% in patients treated with venetoclax with anti‐CD20 antibodies.…”

“…The proportion of patients with antibody response to COVID‐19 vaccines varied from 23% to 47% (Table 1 ) 34 , 35 , 36 , 37 , 38 and was lower compared to patients with other hematologic malignancies and healthy controls. 37 , 38 , 39 , 40 Agha et al 37 showed that patients with CLL were significantly less likely to develop SARS‐CoV‐2 antibodies than patients with other hematologic malignancies (23.1% vs. 61.1%, p = .01). This, in combination with advanced age and other comorbid conditions, put patients with CLL at increased risk of morbidity and mortality from SARS‐CoV‐2 infection, despite the protective role of vaccines in the broad population.…”

mRNA COVID‐19 vaccines in patients with chronic lymphocytic leukemia: A systematic review and meta‐analysis

“…3,5 In agreement with this notion and previous reports, CLL patients are considered to have a heterogeneous and in most instances sub-optimal response to SARS-CoV-2 mRNA vaccines. 3,[6][7][8][9][10][11][12][13][14][15][16][17] Up to now, the response to SARS-CoV-2 mRNA vaccines in CLL patients has been investigated in single-arm and case-control studies. 3,[6][7][8][9][10][11][12][13][14][15][16][17] To assess the strength of the evidence and to better understand the current role of SARS-CoV-2 vaccination in CLL, we conducted a systematic review and meta-analysis using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement (Figure S1).…”

“…3,[6][7][8][9][10][11][12][13][14][15][16][17] Up to now, the response to SARS-CoV-2 mRNA vaccines in CLL patients has been investigated in single-arm and case-control studies. 3,[6][7][8][9][10][11][12][13][14][15][16][17] To assess the strength of the evidence and to better understand the current role of SARS-CoV-2 vaccination in CLL, we conducted a systematic review and meta-analysis using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement (Figure S1). 18 The analysis included all published studies assessing the seroconversion rate in CLL patients after SARS-CoV-2 vaccination consisting of two doses of mRNA vaccine.…”