Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies

Abstract

This study evaluated the safety and immunogenicity of BNT162b2 vaccine in patients with hematological malignancies. Antibodies blocking spike binding to immobilized ACE-2 (NAb) correlated with anti-Spike (S) IgG d42 titers (Spearman r = 0.865, p < 0.0001), and an anti-S IgG d42 level ≥3100 UA/mL was predictive of NAb ≥ 30%, the positivity cutoff for NAb (p < 0.0001). Only 47% of the patients achieved an anti-S IgG d42 level ≥3100 UA/mL after the two BNT162b2 inocula, compared to 87% of healthy controls. In multivariable analysis, male patients, use of B-cell targeting treatment within the last 12 months prior to vaccination, and CD19+ B-cell level <120/uL, were associated with a significantly decreased probability of achieving a protective anti-S IgG level after the second BNT162b2 inoculum. Finally, using the IFN-γ ELISPOT assay, we found a significant increase in T-cell response against the S protein, with 53% of patients having an anti-S IgG-positive ELISPOT after the second BNT162b2 inoculum. There was a correlation between the anti-S ELISPOT response and IgG d42 level (Spearman r = 0.3026, p = 0.012). These findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with hematological malignancies, but only around half of the patients can likely achieve effective immune protection against COVID-19.

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

“…Following title and abstract review, 1,233 records were excluded given that they reported non-original findings, did not include cancer patients, or did not assess COVID-19 vaccines’ immunogenicity. Of the 54 articles that underwent full-text review, 35 articles[ [17] , [18] , [19] , [20] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] ] were considered eligible and were included in the meta-analysis ( Figure 1 ).

Figure 1 The PRISMA flowchart summarizing the process for the identification of eligible studies.

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“…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.

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“…In a subgroup analysis of 13 records evaluating humoral seroconversion rates in patients with hematologic malignancies compared to non-cancer controls, 6 included patients with a partial immunization regimen,[ 20 , 27 , 30 , 44 , 48 , 51 ] 7 with a complete scheme,[ 19 , [32] , [33] , [34] , 40 , 46 , 49 ] and 4 with both partial and complete vaccination. [ 20 , 27 , 30 , 48 ] In the incomplete immunization scheme analysis, of the 997 included participants (523 oncological patients and 474 controls), patients with cancer had a 57% reduced likelihood of achieving an adequate humoral response compared with non-cancer controls (RR 0.43; 95%CI 0.29-0.63).…”

“…A pooled analysis of 6 studies[ 20 , 25 , 26 , 39 , 40 , 54 ] including 84 patients with incomplete and 634 with complete vaccination regimens showed that 78% (95%CI 30-97) and 60% (95%CI 30-84) developed an adequate T-cell response, respectively ( Supplemental eFigure 4 ).…”

Poor neutralization and rapid decay of antibodies to SARS-CoV-2 variants in vaccinated dialysis patients

“…In particular, mRNA-based vaccines developed by Pfizer/BioNTech (BNT-162b2) and Moderna (mRNA-1273) have demonstrated high safety and efficacy in healthy and at-risk individuals, including patients with chronic diseases, cancer and solid organ transplantation [11][12][13][14] . However, immunosuppressed patients, in particular those with hematological malignancies, autoimmune diseases and solid organ transplantations, were shown to mount a low antibody response to these vaccines [15][16][17][18][19][20] . Because of their immunological frailty, patients on dialysis were prioritized in international COVID-19 vaccination programs 21 .…”