Predictors of Poor Seroconversion and Adverse Events to SARS-CoV-2 mRNA BNT162b2 Vaccine in Cancer Patients on Active Treatment

Background: mRNA-based vaccines have shown 95% protection from SARS-COV-2  disease in healthy populations. Initial findings in cancer patients suggest a lower seroconversion and greater toxicity possibly related to myelo-immunosuppressive therapies. Methods: We conducted a prospective study to assess factors predicting poor seroconversion and adverse events following immunization (AEFI) to the BNT162b2 vaccine in cancer patients on active treatment. The primary endpoint was poor seroconversion (IgG 6 months on active surveillance served as controls. Multivariable logistic model and mixed effect models for repeated measures investigated independent factors associated with poor seroconversion and AEFI, adjusting for confounders. Findings: Between March 15 and July 21, 2021, 320 subjects were recruited and 291 were assessable for IgG response. The lack of seroconversion at 42 days was 1.6% (95% CI, 0.4-8.7) on active surveillance, 13.9% (8.2-21.6) on chemotherapy, 11.4% (5.1-21.3) on hormone therapy, 21.7% (7.5-43.7) on biological therapy and 4.8% (0.12-23.8) on immunotherapy. Compared to controls, risk of no IgG response was greater for chemotherapy (P=0.023), biological therapy (0.009) and hormonotherapy (P=0.052). Older age and advanced stage also predicted poor seroconversion. Overall, 43 patients (14.8%) complained of AEFI, mostly of mild grade. Risk of AEFI was greater in females (P=0.001) and younger patients (P=0.009). There was a trend to a D-dimer increase in IgG responders (p=0.01). Interpretation: Except for immunotherapy, chemotherapy, biological therapy and hormone therapy as well as increasing age and advanced stage predict poor seroconversion after two doses of BNT162b2 in up to 20% of patients, indicating the need for a booster dose and long-term serological testing in vaccine non-responders. AEFI occur much more frequently in women and younger subjects who may benefit from preventive medications. Trial Registration: ClinicalTrials.gov Identifier: NCT04932863 Funding: Ospedali Galliera, Associazione WeCare, Lions-Club Genova Sant’Agata. Italian Health Ministry, Ricerca Corrente and 5×1,000 (IEO). Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy, and the local Ethical Committee.