Antibody responses after first and second Covid-19 vaccination in patients with chronic lymphocytic leukaemia

Abstract

B-cell chronic lymphocytic leukaemia (CLL) is associated with immunosuppression and patients are at increased clinical risk following SARS-CoV-2 infection. Covid-19 vaccines offer the potential for protection against severe infection but relatively little is known regarding the profile of the antibody response following first or second vaccination. We studied spike-specific antibody responses following first and/or second Covid-19 vaccination in 299 patients with CLL compared with healthy donors. 286 patients underwent extended interval (10–12 week) vaccination. 154 patients received the BNT162b2 mRNA vaccine and 145 patients received ChAdOx1. Blood samples were taken either by venepuncture or as dried blood spots on filter paper. Spike-specific antibody responses were detectable in 34% of patients with CLL after one vaccine (n = 267) compared to 94% in healthy donors with antibody titres 104-fold lower in the patient group. Antibody responses increased to 75% after second vaccine (n = 55), compared to 100% in healthy donors, although titres remained lower. Multivariate analysis showed that current treatment with BTK inhibitors or IgA deficiency were independently associated with failure to generate an antibody response after the second vaccine. This work supports the need for optimisation of vaccination strategy in patients with CLL including the potential utility of booster vaccines.

Immunogenicity and risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection after Coronavirus Disease 2019 (COVID-19) vaccination in patients with cancer: a systematic review and meta-analysis

“…Of the included 35 studies, 20 reported the seroconversion rate in cancer patients after partial COVID-19 immunization (2574 patients)[ 17 , 20 , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , 37 , [42] , [43] , [44] , [47] , [48] , [49] , [50] , [51] , [52] ] and 24 after complete vaccination schemes (4708 patients). [ [17] , [18] , [19] , [20] , 27 , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , 45 , 46 , 48 , 49 , 53 , 54 ] A lower seroconversion rate was achieved by those with incomplete vaccination regimens (51%; 95%CI 41-62) compared to those with fully immunized patients (73%; 95%CI 64-81) ( P =0.0009) ( Figure 2 ).

Figure 2 Rates of seroconversion in patients with cancer according to vaccination regimen.

…”

Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: The CAPTURE study

“…Given the complete dominance of Delta in the UK and surging prevalence globally, our data on NAb activity against VOCs have contemporary implications for the care of cancer patients who are at increased risk of adverse outcomes of SARS-CoV-2 infection. Studies in cancer patients to date have used seroconversion (i.e., detection of IgG antibodies against WT spike) as the main immunogenicity endpoint [14][15][16][17][18][19][20][21][22][23][24]31 , but NAb against VOCs have not been evaluated. Although we found good concordance between the presence of anti-S1 IgG antibodies and NAbT against WT SARS-CoV-2 in our cohort (in line with reports in those without cancer) [34][35][36] , seroconversion was a poorer surrogate for NAbT against VOCs, where approximately half the patients without detectable NAb against Delta had anti-S1 IgG antibodies.…”

“…Given that cancer or its treatment may impact immunity, characterisation of immune response to COVID-19 vaccines in cancer patients represents a priority. Available studies demonstrated generally high seroconversion rates after two vaccine doses in patients with solid cancers (≥90%, measured as IgG), [14][15][16][17] with less pronounced responses in those with haematological malignancies (compounded by treatments including anti-CD20 therapy) 14,[18][19][20][21][22][23] . However, data on the functionally relevant SARS-CoV-2 neutralising antibody responses, particularly to VOC, are scarce.…”

State of the CAR-T: Risk of Infections with Chimeric Antigen Receptor T-Cell Therapy and Determinants of SARS-CoV-2 Vaccine Responses

“…Diminished vaccine responses have been described in patients with CLL and MM. B-cell depletion, active treatment with BTK inhibitors, and IgA deficiency have been associated with an inadequate humoral response 122 , 123 , 124 , 125 . In the largest study examining patients with HM to date, including 1455 patients, seroprotective antibodies were analyzed 14 days after the second dose of mRNA vaccine.…”