Antibody responses to SARS-CoV-2 vaccination in patients with acute leukaemia and highrisk MDS on active anti-cancer therapies

ABSTRACT

Patients with haematological malignancies, such as acute leukaemia (AL) and high-risk MDS (HRMDS), have significantly increased mortality and morbidity from COVID-19 but vaccine efficacy in these patients remains to be fully established. To date, seroconversion rates following SARS-CoV-2 vaccination in patients with AL and HR-MDS have been reported in small numbers within large retrospective studies, with most not receiving active treatment We characterised the serological responses of patients with AL and HR-MDS who are receiving anti-cancer therapy and were vaccinated within the UK vaccination and programme, receiving two doses of either BNT162b2 or ChAdOx1nCoV-19. Fifty-five patients (35 AML [64%], 14 ALL [25%], 6 HRMDS [11%]), underwent serological testing for anti-S antibody levels after receiving 2 SARS-CoV-2 vaccine doses (71% BNT162b2, 16% ChAdOx1nCoV-19, 13%unknown), between December 2020 and July 2021, Table 1. Serological testing was performed per clinical practice using the Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay (seropositive results being 0.8 U/ml and upper limit >2500 U/ml). The median age was 53 (range 18-76) and 53 patients (96%) were receiving SACT. Serological testing for anti-N antibodies performed on 48 patients (87%) identified 11 (20%) seropositive patients, indicative of previous natural infection. Fifty (91%) were seropositive for anti-S antibodies after two doses (median 43 days [range 4-133] post dose), of these, 33 (60%) were tested following dose 1 (median 36 days [range 24-86]). 76% were seropositive after dose 1, with median antibody titres 7.88 U/ml (IQR 0.7-2.37). This rose to 91% following dose 2, with median 333 U/ml (IQR 27.5-1821). Higher rates of seropositivity are observed in AML/HR-MDS patients (95%) compared to ALL (79%). Patients with AML/HR-MDS also showed a significant increased seropositivity (95%) and titres following dose 2 (median 352 U/ml [IQR 89.95-2116], p = 0.0003), compared to patients with ALL who showed no increase (median 8.395 [IQR 2.335-669.3]). To precisely define seroconversion rates, we excluded patients with anti-N antibodies (indicative of previous SARSCoV-2 infection). SARS-CoV-2 naïve patients with AML/ HR-MDS had higher seroconversion rates and median anti-S antibody titres compared to ALL (median 291 U/ml [IQR 87.03-1771] vs. 5.06 U/ml [1.69-175.6], p = 0.005) and also showed significant increases in titres between post dose 1 and 2 dose titres, not seen in ALL. Patients with previous SARS-CoV-2 infection (anti-N positive) had higher antibody titres, following vaccination in AML/MDS (median 2500 U/ ml [IQR 141-2500]) compared to ALL (median 1541 U/ml [IQR 574.5-2500]), although not statistically significant. There was no significant difference in anti-S antibody response to vaccination in patients treated with intensive or non-intensive AML therapy but significantly reduced anti-S antibody titres were present in patients who received venetoclax-based regimens compared to other therapies ( n = 20, median 158.5 U/ml [IQR 34.85-873] vs. n = 19 median 796 U/ml [IQR 132-2500] p = 0.04). Patients with AML and HR-MDS on SACT are able to generate robust serological responses to SARS-CoV-2 infection but this is not the case for all patients following vaccination. Understanding impact of disease subtypes and therapy on vaccine response is pertinent, as decisions on modifying or delaying treatment in the context of either SARS-CoV-2 infection or vaccination require a clear evidence base. (Table Presented).