Background
Patients with cancer have increased risk of severe outcomes from SARS-CoV-2 infection. Vaccination incompletely reduces risk; vaccinated cancer patients have a higher chance of hospitalisation and death due to COVID-19 than healthy controls. Neutralising antibodies are a correlate of protection. SerOzNET is a prospective study seeking to elucidate nuanced detail about immune response to vaccination in Australians with cancer.
Methods
Participants with cancer were enrolled prior to first SARS-CoV-2 vaccination. Comprehensive information regarding diagnosis and treatment was collected. Blood was sampled at baseline and serial timepoints until 3 months after 5th vaccine dose, and analysed for neutralising antibody response, quantitative IgG response (Abbott), and T-cell cytokine production (IFN-y).
Results
There were 395 patients enrolled, mean age 57 years (range 20-85), 60% were female. Cancer diagnoses were solid organ cancers (SOC) in 257/395 patients (65%), and haematological cancers (HC) in 138/395 (35%). Cytotoxic chemotherapy was received by 49% of SOC and 62% of HC patients. Neutralising antibody was detectable in SOC and HC respectively in 84% and 43% after 2 doses, 96% and 65% after 3 doses, 98% and 69% after 4 doses and 100% and 90% after 5 doses. T cell IFNγ response was detected in SOC and HC respectively in 72% and 49% after 2 doses, 75% and 90% after 3 doses and 82% and 87% after 4 doses. On multivariate analysis, antibody response rate was higher in SOC (vs HC, OR 1.38, 1.06-1.8, p=0.017), and lower in patients on anti-B cell therapies (OR 0.19, 0.13-0.27, p<0.001). T cell response was predicted by SOC (vs HC, OR 1.76, 1.27-1.43, p=0.001). There was a non-significant trend toward negative effect of chemotherapy on antibody (OR 0.81, 0.64-1.03) and T cell response (OR 0.8, 0.6-1.06). Median absolute IgG titre was lower at serial timepoints in patients with HC, or on steroids, and higher with hybrid immunity post infection. B cell count correlated with IgG titre and was lower in patients on anti-B-cell therapies.
Conclusion
Most patients with cancer develop protective antibodies after SARS-CoV-2 vaccination, proportion of responders increases after each dose. After 3 doses, almost all patients with SOC respond however a third of HC patients do not. T cell response may provide an additional means of protection for patients with suboptimal antibody response; however, HC patients have reduced T cell and antibody response, placing them at higher risk. Patients with HC may require additional boosters and precautions against SARS-CoV-2 infection.