Immunogenicity of the mRNA-1273 SARS-CoV-2 vaccine in cancer patients receiving immunotherapy agents

BackgroundLittle is known about the influence of different anticancer therapies in the immunogenicity, efficacy, and safety of SARS-CoV-2 vaccines. Particularly, Immunotherapy could increase the rate of response to COVID-19 vaccines, counteracting cancer immunosuppression and restoring T-cell competence.MethodsWe conducted an observational study to assess the immunogenicity of mRNA-1273 SARS-CoV-2 vaccination in patients with solid tumours treated with immunotherapy. Blood samples were collected to analyse the humoral (specific anti-spike IgG) and cellular response (IFN-g producing CD4+ and CD8+ T-cells after stimulation with structural viral proteins) at baseline (BL), after the first vaccine dose (1D) and after the second vaccine dose (2D). Patients with previous COVID-19 or positive serology were excluded.ResultsThe characteristics of the 25 patients included were: median age 65.9 years (IQR 56.2 – 72.8); 48% female; 28% with genitourinary tumours, 20% melanoma, 16% lung cancer and 36% with other tumours; 92% stage IV; treatment with anti-PD1 in 64%, with anti-PDL1 in 24% and with a combination of anti-CTLA4 plus anti-PD1/PDL1 in 12%. Median anti-spike (S) IgG titres were 0.95 AU/ml (IQR 0.3 – 23.3) at BL, 544.2 (IQR 239 – 995.5) after 1D and 14238.1 (IQR 8570.3 – 28717.9) after 2D. Humoral response (cut-off point = 50 AU/ml) was significantly improved reaching 94.4% after 1D and 100% after 2D (p<0.001). Of note, cellular response at BL was found in 20% and 25% for CD4+ and CD8+ anti-S T-cells respectively, suggesting cross-reactivity. After 2D of vaccine, CD4+ and CD8+ T-cell response was observed in 58.8% (p=0.01) and 64.7% (p=0.03), respectively. Nevertheless, after excluding patients with previous positive serology or/and cross-reactive cellular response, only 41.7% and 58.3% had CD4+ or CD8+ anti-S T-cell response, respectively. Overall, there were no severe reactions to the vaccine.ConclusionsOur study shows that patients with solid tumours treated with immunotherapy agents achieve a robust humoral response but, contrary to what was expected, poor cellular response against SARS-CoV-2 after full vaccination. Alternative treatment strategies are needed to improve the immunogenicity of SARS-CoV2 vaccines for these patients.Legal entity responsible for the studyRamón y Cajal Institute for Health Research (IRYCIS).FundingRamón y Cajal Institute for Health Research (IRYCIS).DisclosureAll authors have declared no conflicts of interest. BackgroundLittle is known about the influence of different anticancer therapies in the immunogenicity, efficacy, and safety of SARS-CoV-2 vaccines. Particularly, Immunotherapy could increase the rate of response to COVID-19 vaccines, counteracting cancer immunosuppression and restoring T-cell competence. Little is known about the influence of different anticancer therapies in the immunogenicity, efficacy, and safety of SARS-CoV-2 vaccines. Particularly, Immunotherapy could increase the rate of response to COVID-19 vaccines, counteracting cancer immunosuppression and restoring T-cell competence. MethodsWe conducted an observational study to assess the immunogenicity of mRNA-1273 SARS-CoV-2 vaccination in patients with solid tumours treated with immunotherapy. Blood samples were collected to analyse the humoral (specific anti-spike IgG) and cellular response (IFN-g producing CD4+ and CD8+ T-cells after stimulation with structural viral proteins) at baseline (BL), after the first vaccine dose (1D) and after the second vaccine dose (2D). Patients with previous COVID-19 or positive serology were excluded. We conducted an observational study to assess the immunogenicity of mRNA-1273 SARS-CoV-2 vaccination in patients with solid tumours treated with immunotherapy. Blood samples were collected to analyse the humoral (specific anti-spike IgG) and cellular response (IFN-g producing CD4+ and CD8+ T-cells after stimulation with structural viral proteins) at baseline (BL), after the first vaccine dose (1D) and after the second vaccine dose (2D). Patients with previous COVID-19 or positive serology were excluded. ResultsThe characteristics of the 25 patients included were: median age 65.9 years (IQR 56.2 – 72.8); 48% female; 28% with genitourinary tumours, 20% melanoma, 16% lung cancer and 36% with other tumours; 92% stage IV; treatment with anti-PD1 in 64%, with anti-PDL1 in 24% and with a combination of anti-CTLA4 plus anti-PD1/PDL1 in 12%. Median anti-spike (S) IgG titres were 0.95 AU/ml (IQR 0.3 – 23.3) at BL, 544.2 (IQR 239 – 995.5) after 1D and 14238.1 (IQR 8570.3 – 28717.9) after 2D. Humoral response (cut-off point = 50 AU/ml) was significantly improved reaching 94.4% after 1D and 100% after 2D (p<0.001). Of note, cellular response at BL was found in 20% and 25% for CD4+ and CD8+ anti-S T-cells respectively, suggesting cross-reactivity. After 2D of vaccine, CD4+ and CD8+ T-cell response was observed in 58.8% (p=0.01) and 64.7% (p=0.03), respectively. Nevertheless, after excluding patients with previous positive serology or/and cross-reactive cellular response, only 41.7% and 58.3% had CD4+ or CD8+ anti-S T-cell response, respectively. Overall, there were no severe reactions to the vaccine. The characteristics of the 25 patients included were: median age 65.9 years (IQR 56.2 – 72.8); 48% female; 28% with genitourinary tumours, 20% melanoma, 16% lung cancer and 36% with other tumours; 92% stage IV; treatment with anti-PD1 in 64%, with anti-PDL1 in 24% and with a combination of anti-CTLA4 plus anti-PD1/PDL1 in 12%. Median anti-spike (S) IgG titres were 0.95 AU/ml (IQR 0.3 – 23.3) at BL, 544.2 (IQR 239 – 995.5) after 1D and 14238.1 (IQR 8570.3 – 28717.9) after 2D. Humoral response (cut-off point = 50 AU/ml) was significantly improved reaching 94.4% after 1D and 100% after 2D (p<0.001). Of note, cellular response at BL was found in 20% and 25% for CD4+ and CD8+ anti-S T-cells respectively, suggesting cross-reactivity. After 2D of vaccine, CD4+ and CD8+ T-cell response was observed in 58.8% (p=0.01) and 64.7% (p=0.03), respectively. Nevertheless, after excluding patients with previous positive serology or/and cross-reactive cellular response, only 41.7% and 58.3% had CD4+ or CD8+ anti-S T-cell response, respectively. Overall, there were no severe reactions to the vaccine. ConclusionsOur study shows that patients with solid tumours treated with immunotherapy agents achieve a robust humoral response but, contrary to what was expected, poor cellular response against SARS-CoV-2 after full vaccination. Alternative treatment strategies are needed to improve the immunogenicity of SARS-CoV2 vaccines for these patients. Our study shows that patients with solid tumours treated with immunotherapy agents achieve a robust humoral response but, contrary to what was expected, poor cellular response against SARS-CoV-2 after full vaccination. Alternative treatment strategies are needed to improve the immunogenicity of SARS-CoV2 vaccines for these patients.