OAB-047: Plasma cell disorder patients are left vulnerable after one dose of the BNT162b2 mRNA or the ChAdOx-nCOV-19 COVID-19 vaccines

BACKGROUND: Concerns have been raised about the ability of patients with plasma cell disorders (PCD) to mount adequate immune responses to vaccination, particularly considering the initial extension to vaccination intervals in the United Kingdom to up to 12 weeks in December 2020, the start of the vaccination roll-out. Protecting this vulnerable patient group with anti-SARS-CoV-2 vaccination is critical. METHODS: We measured the humoral responses in PCD patients after the first dose of the BNT162b2 and ChAdOx-1 nCOV-19 vaccines. Antibody levels were measured using Elecsys Anti-SARS-CoV-2S assay for quantitative detection of IgG Abs, specific for the SARS-CoV-2 spike-protein receptor binding domain. Positive cut-off of ≥0.80 U/mL defined serologic response. Testing was performed at (or closest to) 4 and 8 weeks post-dose. Baseline nucleocapsid Ab results were available from previous screening in a subset of patients. Clinical information was retrieved from medical records. RESULTS: 198 PCD patients (178 multiple myeloma, 15 amyloid, 3 SMM/MGUS, other 2 PCD), median age 63 (range 35-84), had serologic assessment after one vaccine dose against SARS-CoV-2. 69% (138) were on chemo-immunotherapy treatment (CIT) within 4 weeks of first dose. Previous COVID-19 infection and exposure was defined as a positive COVID-19 PCR swab or positive N-antibody at baseline and were excluded from analysis. Patients were tested at median 42 days (range 11-90) after their first dose. After one dose, 68% (135/198) were seropositive, with median Ab titres 21 U/mL (IQR 3.92-133.5). In those with negative baseline Ab test, seroconversion to one dose was 67% (64/96). Forty-one patients were tested more than once after one dose, at median 33 days (12-62) and again at 67 days (38-91). 22 were seronegative at first testing, of these, 6 seroconverted on second testing, prior to second dose. Age ≥70, light chain (LC) disease, disease status less than VGPR, CIT within 4 weeks, low IgM and ASCT more than 12m were statistically significant seronegative predictors on univariate analyses. LC disease, less than VGPR and IgM less than 0.4g/L, retained statistical significance on multivariate analyses. On linear regression analysis in seropositive patients, more lines of treatment and CIT within 4 weeks were significantly associated with lower antibody titres. CONCLUSION: Serologic response to SARS-CoV-2 vaccination is lower in PCD patients than reported healthy controls at 68% after one dose. Further work in PCD is needed to understand how Ab levels correlate to neutralisation capability, cellular responses, protection from infection and how long seroconversion lasts to better define correlates of protection. Nearly a third do not respond to a single vaccine dose causing concerns that PCD patients are left vulnerable with a delayed vaccination strategy and should be prioritised to receiving the second dose at the recommended manufacturers time scale of 3 or 4 weeks.