Patients with plasma cell disorders retain their humoral response to COVID-19 vaccination following autologous stem cell transplant but falling titres emphasise the importance of re-vaccination

ABSTRACT

There is increased infection risk at the time of autologous stem cell transplantation (ASCT) including for patients with plasma cell disorders (PCD), therefore preventing infection with COVID-19 vaccination in this vulnerable group is key. However, patients with PCD have been shown to mount suboptimal responses to COVID-19 vaccination. A clinical audit of serological response to COVID-19 vaccination before and after ASCT was undertaken, to observe how antibody titres change during this period. Antibodies to the SARS-CoV-2 spike protein were measured using the Elecsys Anti-SARS-CoV-2S assay (Roche diagnostics) in 88 patients who underwent ASCT for PCD at the University College London Hospital NHS Foundation Trust between December 2020 and September 2021. Pre-ASCT antibody titres were measured following first or second vaccine and following ASCT. The majority ( n = 76) had no prior history of COVID-19 infection, and four of this cohort declined vaccination. In those who received one vaccine pre-ASCT ( n = 21), 76% seroconverted with a median titre of 11.3 3 U/ml (IQR 1.5-62.6). In those who received two doses pre-ASCT ( n = 51), 97% seroconverted with a median titre of 494 U/ml (IQR 190.5-1681). In those who received two doses pre-ASCT, anti-S antibodies were detected in the immediate post-ASCT setting, with titres of 373 U/ml (median, IQR 40.6-2326) measured less than or equal to 28 days (median 15 [6-25]) post-ASCT, and 170 U/ml (IQR 55-604) at more than 28 days (median 85 [32-125]) post-ASCT. Patients who received one dose pre-ASCT had lower median titres of 36.5 U/ml (IQR 12.6-1310) measured less than or equal to 28 days (median 15 [12-22] post-ASCT and 7.7 U/ml (IQR 2.9-23.8) at more than 28 days (median 85 [40-104] post-ASCT. Antibody levels declined over time, but patients who had received two vaccines pre-ASCT maintained higher titres post-ASCT compared to those who had received one dose, emphasising the importance of COVID-19 vaccination prior to ASCT. Our patients are advised to be re-vaccinated against COVID-19 3 months after ASCT, and antibody response following re-vaccination was measured in a subgroup ( n = 14). Those who were previously un-vaccinated did not seroconvert following one dose. However, antibody titres in those who had received either one or two vaccines ( n = 12) prior to ASCT increased from 32.4 U/ml (median, IQR 13.4-1082) post-ASCT to 431 U/ml (median, IQR 15.33-2500) following re-vaccination. Those who had received two vaccines pre-ASCT ( n = 2) achieved higher titres than those who had received a single dose. In conclusion, we demonstrated how protective titres fall during the patient's journey through ASCT and our repeated interactions with them. Despite this, patients vaccinated prior to ASCT maintain some level of measurable antibody immediately post-ASCT, which is encouraging as patients are considered most vulnerable to infection during this period. Titres were also boosted effectively after one dose of re-vaccination, compared to those never vaccinated. Current guidance is for adult patients who have undergone ASCT to be considered 'never vaccinated' against COVID-19, in line with pre-COVID-19 re-vaccination practice, and to receive a three-dose primary course followed by a booster vaccination post-ASCT. We must facilitate and encourage our patients to be vaccinated prior and after ASCT in this rapidly changing landscape, especially in context of the spread and evolution of a potentially more transmissible virus. (Table Presented).