Comprehensive humoral and cellular immune responses to COVID-19 vaccination in adults with cancer

Background: The COVID-19 pandemic has significantly impacted people with cancer. Initial vaccine studies excluded patients with malignancy. Immunocompromised individuals remain vulnerable to SARS-CoV-2, necessitating detailed understanding of vaccine response. The epidemiology of COVID-19 in Australia offered unique opportunities to study cancer populations with minimal community exposure to SARS-CoV-2. Methods: SerOzNET prospectively examined previously unvaccinated patients with solid and haematological malignancies receiving up to five COVID-19 vaccine doses. Antibody response was measured by live virus neutralisation assay (neutralising antibody (NAb); positive titre >= 1:20; study primary endpoint) and commercial assay. T cell response was measured by cytometric bead array; positive defined as interferon gamma (IFN-gamma) >= 10 pg/mL in response to Spike antigen. Patient and physician-reported adverse events were secondary endpoints. Outcomes: 395 adults were enrolled prior to receiving mRNA vaccine (BNT162b2 = 347; mRNA-1273 = 1) or viral vector vaccine (ChadOx1-S = 43) for initial two-dose course, plus up to three additional doses. Median age was 58 years (range: 20-85); 60 % were female; 35 % had haematological malignancy, 2/395 (0.5 %) had baseline positive nucleocapsid antibody indicating prior SARS-CoV-2 exposure. NAb response post dose three was demonstrated in 84 % overall; 96 % of patients with solid cancers and 64 % with haematological cancer (p < 0.001). Risk factors for non-response were haematological cancer and anti B-cell therapies. Some patients with haematological cancer seroconverted for the first time after the fourth or fifth dose. IFN-gamma response was seen in many patients with haematological cancer who lacked NAb response. Serious adverse events were rare. COVID19 infection occurred in 29 % with no deaths. Interpretation: COVID-19 vaccination elicits B and T cell responses in patients with solid and haematological cancers, with an acceptable safety profile. A significant proportion of haematological cancer patients require >3 doses to elicit NAb, with many demonstrating T cell response, which may be an alternative pathway of immune protection.