Longitudinal efficacy and toxicity of SARS-CoV-2 vaccination in cancer patients treated with immunotherapy

Abstract

Abstract Background Despite more than 2 years having elapsed since the onset of SARS-CoV-2 pandemic, a level of hesitation around increased SARS-CoV-2 vaccine toxicity in cancer patients receiving immunotherapy (IO) remains. Here, we explore serological responses to SARS-CoV-2 vaccination in patients treated with IO and we describe blood cytokines, autoantibody levels and immune-related adverse events (irAEs) post vaccination. Methods Serum anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) antibodies, surrogate viral neutralization test (sVNT), Th1/Th2 cytokines and antibodies against self-antigens were quantified at baseline, between 1st and 2nd vaccine doses, at 1 week (1W), 1 month (1M), 4–6 months and 10–12 months after the 2nd dose. Grade 2 or higher (≥ gr2+) irAEs were captured prospectively. Results Fifty-one evaluable patients were enrolled in this longitudinal study, 35 on immunotherapy (IO) and 16 on non-immunotherapy (non-IO) treatment. Absolute levels and neutralization potential of anti-SARS-CoV-2 antibodies were not significantly different in the IO group compared to non-IO. Chemotherapy adversely affects seroconversion when compared to IO and/or targeted treatment with antibody levels of 67.6 U/mL vs 1441 U/mL (p = 0.006) and sVNT of 70.9% vs 94.5% (p = 0.009), at 1M after 2nd vaccine dose. Following vaccination, the prevalence of grade ≥ 2 irAEs in patients treated with IO was not higher than the usual reported IO toxicity. We report, for the first time, that post-vaccination, IgM autoantibodies against beta 2 glycoprotein (p = 0.02), myeloperoxidase (p = 0.03), nucleosome (p = 0.041), SPLUNC2 (p < 0.001) and IgG autoantibody against Myosin Heavy Chain 6 (MYH6) (p < 0.001), were significantly elevated and this increase was unrelated to the type of treatment. Discussion Comprehensive analysis of a small cohort showed that co-administration of SARS-CoV-2 vaccine and IO is not associated with increased irAEs. The detection of autoantibodies post anti-SARS-CoV-2 vaccination warrants further investigation. (NCT03702309)