key: cord-1043378-gu84z3kr authors: Giugliano, Federica; Zucali, Paolo Andrea; Galli, Giulia; Ballatore, Zelmira; Corti, Chiara; Aliaga, Pamela Trillo; Uliano, Jacopo; Vivanet, Grazia; Curigliano, Giuseppe; Conforti, Fabio; Queirolo, Paola; Berardi, Rossana; Manglaviti, Sara; Apollonio, Giulia; Perrino, Matteo; Borea, Federica; D'Antonio, Federica; Garassino, Marina Chiara; De Pas, Tommaso title: SARS-CoV-2 Vaccine in Patients with Thymic Epithelial Tumours with and without active or pre-existing autoimmune disorders: brief report of a TYME Network safety analysis date: 2022-02-25 journal: Eur J Cancer DOI: 10.1016/j.ejca.2022.02.011 sha: 59f541280ba3f9e2f64e0c791e37f8a8d5763abf doc_id: 1043378 cord_uid: gu84z3kr BACKGROUND: International guidelines recommend SARS-CoV-2 Vaccine for patients with cancer. A substantial risk of developing vaccine-related autoimmune toxicities could be hypothesized for patients with Thymic Epithelial Tumours (TETs) due to their high risk of autoimmune disorders (ADs). Moreover, a cross-reaction between SARS-CoV-2 spike protein antibodies and various tissue proteins has been shown, and antibodies against nucleoproteins showed overlaps in the autoimmune cross-reaction with antibodies to spike protein. Due to the rarity of TETs, no data addressing this hypothesis are available. METHODS: Patients with TETs who received SARS-CoV2 vaccine, treated in 4 referral centers of the Italian Collaborative Group for ThYmic MalignanciEs (TYME) network between February 2021 and September 2021, were interviewed through a standardized 15-items questionnaire, in order to describe the safety of SARS-CoV-2 Vaccine in patients affected by TETs. RESULTS: Data from 245 doses of vaccine administered to 126 patients (41 = thymic carcinoma, 85 = thymoma; 38 with AD of which 26 with active AD) were collected. Nine patients had a previous COVID-19 positive swab. No cases of AD reactivation or worsening of a preexisting AD were seen in the study population. New diagnosis of myasthenia gravis likely unrelated to vaccine was made in two patients after the vaccination. Sixty-four patients (51%) experienced a total of 103 Adverse Events, all G1/G2, most commonly fatigue, new or worsening muscle pain and chills. None AE required patients’ hospitalization. CONCLUSIONS: SARS-CoV-2 mRNA-vaccines appear to be safe in patients with TET, even in case of active or pre-existing AD. The remaining authors declare nothing to disclose. 47 Background: International guidelines recommend SARS-CoV-2 Vaccine for patients with cancer. 52 A substantial risk of developing vaccine-related autoimmune toxicities could be hypothesized for 53 patients with Thymic Epithelial Tumours (TETs) due to their high risk of autoimmune disorders 54 (ADs). Moreover, a cross-reaction between SARS-CoV-2 spike protein antibodies and various 55 tissue proteins has been shown, and antibodies against nucleoproteins showed overlaps in the 56 autoimmune cross-reaction with antibodies to spike protein. Due to the rarity of TETs, no data 57 addressing this hypothesis are available. International guidelines recommend severe acute respiratory syndrome coronavirus 2 (SARS-CoV-80 2) Vaccine for patients with cancer. A substantial risk of developing vaccine-related autoimmune 81 toxicities could be hypothesized for patients with Thymic Epithelial Tumours (TETs) due to their 82 higher risk of autoimmune disorders (ADs) and to the anecdotally reported AD flares temporally 83 associated with SARS-CoV-2 Vaccine. 1-5 84 Moreover, a cross-reaction between SARS-CoV-2 spike protein antibodies and various tissue 85 proteins has been showed, and antibodies against nucleoproteins showed overlaps in the 86 autoimmune cross-reaction with antibodies to spike protein 6 . 87 Due to the rarity of TETs and to the exclusion of patients with active cancer from most randomized 88 COVID-19 vaccine clinical trials 7-9 , no data addressing this hypothesis are available. 89 To address this issue, we interviewed through a standardized 15-items questionnaire patients with 90 TETs, treated in 4 referral centers of the Italian Collaborative Group for ThYmic MalignanciEs 91 (TYME) who received SARS-CoV2 vaccine between February 2021 and September 2021. 10 92 93 All patients aged 18 years old or more with pathologically-confirmed diagnosis of TET (any stage) 96 who received at least one dose of SARS-CoV-2 vaccine were identified in 4 referral centers of 97 TYME network. 98 Patients who received vaccine between February 2021 and September 2021 (minimum follow up: 99 Primary outcomes were AE rate and incidence of new ADs or worsening of preexisting AD in the 108 examined population. 109 Statistical analysis was performed using R Statistical Software (version 4.1.2; R Foundation for 110 Statistical Computing, Vienna, Austria). 111 Results 113 The clinical features of 126 patients affected by TET are summarized in Table 1 and Table 2 . Nine patients (7%) referred a positive swab for SARS-CoV-2 in the last 12 months (Table A. 2), of 119 which 7 (5%) reported COVID-19 symptoms. Oxygen therapy and/or hospitalization were required 120 for 4 patients. 121 Overall, 245 doses of vaccine were administered to 126 patients. All patients received at least one 122 dose of SARS-CoV-2 vaccine, and 118 (94%) completed the cycle with the second dose. One 123 patient received also a third dose (booster dose). One-hundred-twenty-one (96%) patients 124 received a mRNA-based vaccination, namely COMIRNATY® (Pfizer) (n = 105) or SPIVAX® 125 (Moderna) (n = 16). (Table A. 3) 126 2.7%-13.5%), vomiting (n = 2; 1.9%, 95%CI 2.4%-6.8%), diarrhea (n = 2; 1.9%, 95%CI 2.4%-6.8%) 136 and other (n = 7; 6.8%, 95%CI 2.7%-13.5%). The most common G2 event was fever (n = 2; 1.9%, 137 95%CI 2.4%-6.8%) and new or worsening muscle pain (n = 2, 1.9%, 95%CI 2.4%-6.8%). The 138 majority (n = 100; 97%, 95%CI 91.7%-99.4%) of AEs started within 7 days from vaccination and 139 last 1 to 3 days (n = 84; 81.5%, 95%CI 72.7%-88.5%). 17 AE required outpatient systemic 140 pharmacologic intervention, namely fever (n = 6), fatigue (n = 2), chills (n = 2), muscle pain (n = 3), 141 joint pain (n = 2), vomiting (n = 1), other (n = 1). None of the patients were hospitalized due to AEs. -Thymic Epithelial Tumours (TETs) induce higher risk for autoimmune diseases -Evidence on safety profile of COVID vaccines in TET patients is limited -Our data suggest that safety profile for TET patients is similar to general population -COVID-19 vaccination is safe and strongly recommended in patients affected by TET J o u r n a l P r e -p r o o f Epidemiology of Thymoma and Associated Malignancies A Case of COVID-19 Vaccine Causing a 190 A practical approach for vaccinations including COVID-193 19 in autoimmune/autoinflammatory rheumatic diseases: a non-systematic review AstraZeneca (AZD1222) COVID-19 vaccine-196 associated adverse drug event: A case report Reaction of Human Monoclonal Antibodies to SARS CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases Phase 3 Safety and Efficacy of AZD1222 202 (ChAdOx1 nCoV-19) Covid-19 Vaccine Safety and Efficacy of the BNT162b2 mRNA 205 Covid-19 Vaccine through 6 Months Efficacy and Safety of the mRNA-1273 SARS-CoV-208 Federica Giugliano: Conceptualization; Data curation; Formal analysis; Investigation; Methodology Project administration; Software; Supervision; Validation; Visualization; Roles/Writing -original draft Data curation; Formal analysis; Investigation, Validation; Visualization Writing -review & editing Data curation; Formal analysis; Investigation, Validation; Visualization; Writing -review & editing Data curation; Formal analysis; Investigation, Validation; Visualization; Writingreview & editing Data curation; Validation; Roles/Writing -original draft; Writing -review & editing Pamela Trillo: Aliaga: Data curation Data curation; Formal analysis; Investigation; Methodology; Writing -review & editing Data curation; Formal analysis; Investigation; Methodology; Writing -review & editing Giuseppe Curigliano: Validation Writing -review & editing Conforti : Conceptualization; Data curation; Formal analysis; Investigation; Methodology Project administration; Resources; Software; Supervision; Validation; Visualization; Roles/Writingoriginal draft Writing -review & editing, Rossana Berardi: : Data curation; Formal analysis; Investigation, Validation; Visualization Roles/Writing -original draft; Writing -review & editing Data curation; Formal analysis; Investigation, Validation; Visualization Roles/Writing -original draft Data curation; Formal analysis; Investigation, Validation; Visualization; Writingreview & editing Data curation; Formal analysis; Investigation, Validation; Visualization; Writingreview & editing Data curation; Formal analysis; Investigation, Validation; Visualization Data curation; Formal analysis; Investigation, Validation; Visualization; Writing -review & editing Marina Chiara Garassino : Data curation; Formal analysis; Investigation, Validation; Visualization Writing -review & editing Tommaso De Pas: Conceptualization; Data curation; Formal analysis; Investigation; Methodology Project administration; Resources; Software; Supervision; Validation; Visualization; Roles/Writingoriginal draft ☐ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work ☒The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Disclosure: PAZ declare Consulting or Advisory Role for Astellas Pharma; AstraZeneca Foundation Medicine; she has received research funding from the following organizations: AIRC, AIFA, Italian Moh, TRANSCAN. GMC declares personal fees from MSD, AstraZeneca, Eli Lilly and BMS, outside the submitted work. RB is a consultant/advisory board member for Astra Zeneca