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

Patients with haematological malignancies, such as acute leukaemia and high-risk MDS (HR-MDS), have significantly increased mortality and morbidity from COVID-19. However vaccine efficacy in these patients and the impact of systemic anti-cancer therapy (SACT) on vaccine response remains to be fully established. SARS-CoV-2 antibody responses in 53 patients with ALL, AML or HR-MDS receiving SACT were characterised following two doses of either BNT162b2 or ChAdOx1nCoV-19. All patients were tested for anti-S antibodies after 2 doses, 60% after the first dose and anti-N antibody testing was performed on 46 patients (87%). Seropositivity rates after 2 vaccine doses were 95% in AML/HR-MDS patients and 79% in ALL. After stratification by prior SARS-CoV-2 infection, naïve patients with AML/HR-MDS had higher seroconversion rates and median anti-S antibody titres compared to ALL (median 291U/mL versus 5.06U/mL), and significant increases in anti-S titres with consecutive vaccine doses, not seen in ALL. No difference was seen in serological response between patients receiving intensive chemotherapy or non-intensive therapies (HMA) but significantly reduced titres were present in AML/HR-MDS patients who received venetoclax-based regimens compared to other therapies. All ALL patients received intensive chemotherapy, with no further impact of anti-CD20 immunotherapy on serological response. Understanding the impact of disease subtypes and therapy on vaccine response is essential to enable decisions on modifying or delaying treatment in the context of either SARS-CoV-2 infection or vaccination.