ABSTRACT
Background: Thymic epithelial tumors (TETs) are rare malignancies associated with dysregulation of the immune system with humoral and cell mediated immunity abnormalities. Anti-syndrome coronavirus type 2 (SARSCoV- 2) vaccine is effective at preventing COVID-19 morbidity and mortality. No published data are available regarding the post-vaccine immunization in TET patients (pts). The aim of our study was to evaluate the immunization in TET pts, who received the third mRNA vaccine dose and who did not achieve seroconversion after the previous two doses. Method(s): Starting from November 2021 to March 2022, 23 consecutive TET patients (pts) found to be serologically negative after two doses of SARS-Cov-2 mRNA vaccine (BNT162b2 by Pfizer-BioNTech) were enrolled at the Rare Tumors Coordinating Center of Campania Region (CRCTR-Naples, Italy). SARS-CoV-2 spike-binding IgG antibody serological levels were centrally analyzed by chemiluminescent immunoassay (CLIA) at two different time-points: T0 (before the third dose) and T1 (one month after the third dose). Cut-off for Ab titers positivity was >25 AU/mL. Result(s): Among the 23 enrolled pts, 10 (43,5%) were female and 13 (56,5%) males;17 pts had thymoma and 6 thymic carcinoma. Autoimmune disorders were detected in 20 TET pts (87%), of whom 3 (15%) suffered from Myasthenia Gravis, 8 (40%) from Good's Syndrome, 7 (35%) from both diseases, and 2 (10%) from other autoimmune disorders. By the time of third vaccine dose 2 pts had died, 2 pts were lost to follow up, 5 pts had suffered from SARS-CoV-2 infection. Of the remaining 14 pts, 7 achieved seroconversion whereas 7 maintained negative serological antibody titers. Two of these 7 pts had SARSCoV- 2 infection after the third dose. Interestingly, among these 7 pts who did not develop positive antibody titers, 6 had active cancer disease and only one was diseasefree. Moreover, 6 out of these 7 pts suffered from Good's Syndrome. On the other hand, among the 7 pts who developed positive antibody titers, only 3 had active disease. Conclusion(s): Our preliminary results showed that TET pts who did not achieve seroconversion even after the third SARS-Cov-2 vaccine dose in most cases had active cancer disease. If confirmed on larger cohorts of patients, these data may have important clinical implications and may help to better identify fragile pts who could benefit the most from prophylactic therapy with monoclonal antibodies.
ABSTRACT
Background: Thymic epithelial tumors (TET) are rare malignancies associated with dysregulation of the immune system and humoral and cell mediated immunity abnormalities. Anti-syndrome coronavirus type 2 (SARS-CoV-2) vaccine is effective at preventing COVID-19 morbidity and mortality. No published data are available regarding the immunization in TET patients (pts). The aim of this study was to evaluate the immunization in TET pts who received two doses of mRNA vaccine, by longitudinal serological detection of SARS-COV-2 spike-binding IgG antibody. Methods: Starting from April 2021 to October 2021, consecutive TET pts referred to the Rare Tumors Coordinating Center of Campania Region (CRCTR - Naples, Italy) were enrolled. All study subjects received two doses of COVID-19 mRNA vaccine (BNT162b2 by Pfizer-BioNTech). SARS-CoV-2 spike-binding IgG antibody (Ab) serological levels were analyzed by centralized chemiluminescent immunoassay (CLIA) at different time-points, including before 1st vaccine dose (T0) and 1 month after 2nd dose (T2). Cut-off for Ab titers positivity was > 25 AU/mL. Results: Forty pts were enrolled;23 (57.5%) were female and 17 (42.5%) male. Eleven pts (27.5%) suffered from thymic carcinoma, 28 (70%) thymoma, and 1 (2.5%) thymic hyperplasia. At the time of study enrollment, 20 pts (50%) had no evidence of disease (NED) and were in followup;the remaining 20 pts had evidence of disease (ED) by imaging and were receiving systemic treatment (55% oral low-dose etoposide-based therapy, 40% somatostatin analogs + prednisone, 5% supportive care). Immune system disorders were diagnosed in 29 TET pts (72.5%): 19 pts (47.5%) had Good's Syndrome (GS) and 10 (25%) other immune disorders. At T0, all enrolled pts had negative Ab titers and no prior SARS-CoV-2 infection. At T2, Ab data were available for 37 pts (92.5%): 18 pts (48.7%) had positive Ab titers, whereas 19 (51.3%) did not achieve seroconversion. Among pts with ED, seroconversion was achieved only in 2 cases (11.8%). Lack of seroconversion at T2 was significantly associated with ED (Fisher's exact test p: 0.0001) and with the presence of GS (Fisher's exact test p: 0.0489). No significant association of seroconversion with other immune disorders and disease features was found. Conclusions: Our data showed that TET pts with ED had substantially higher probability of impaired seroconversion after SARS-COV-2 vaccine as compared with NED pts. We warrant further studies to evaluate the role of disease status, anti-tumor treatments and immune disorders in post-vaccine immunization of TET pts.