Prevalence of autoimmune diseases in thymic epithelial tumors (TET) insights from RYTHMIC.

Abstract

9073 Background: TET are associated with autoimmune disorders (AID) in up to 30% of patients (pts). However, there have been wide variations in the reported prevalence of AID in TET pts in small single-center series. RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French network mandated to systematically discuss every case of TET. We aimed to describe the prevalence of AID in a large French population. Methods: RYTHMIC database, hosted by IFCT (Intergroupe Francophone de Cancérologie Thoracique), prospectively includes all consecutive pts with a diagnosis of TET discussed in French national or regional tumor boards. We analyzed epidemiologic, clinical and pathological characteristics of pts with TET’s related AID. Results: From January 2012 to December 2019, 2909 pts were included in the database. The mean age at diagnosis of TET was 54 and 52% were male. In the overall population, Masaoka Koga stages were well balanced with 12.6% (n = 187) stage I, 8.8% (n = 131) stage IIa, 8.4% (n = 124) stage IIb, 11.1% (n = 164) stage III and 8.5% (n = 125) stage IV. There were 364 (12.5%) events of AID in 302 pts. 62 pts (17%) had more than 1 AID. Among the events, 236 were myasthenia gravis (MG) (64.8%), 19 Hypo-gammaglobulinemia syndrome (5.2%), 15 pure red cell aplasia (4.1%), 18 thyroiditis (4.9%) and 16 systemic erythematous lupus (4.4%). Diagnosis of AID was mostly done at tumor diagnosis (n = 239, 65.7%) but some patient had AID diagnosed before diagnosis (n = 67, 18.4%) or during follow up (n = 32, 8.8%). Among pts presenting AID, B2 was the most common subtype (n = 133, 36.5%). The incidence of AID per subtype was as follow: A (n = 10/81, 12.3%), AB (n = 48/225, 21.3%), B1 (n = 35/130, 26.9%), B2 (n = 133/295, 45.0%), B3 (n = 46/113, 40.7%), thymic carcinoma (n = 16/275, 5.8%). Conclusions: The prevalence of AID in pts with TET was 12.5%, > 40% in B2 and B3 subtypes. Diagnosis of AID can be delayed compared to the diagnosis of TET. Immunotherapy indication should be carefully assessed in pts with TET other than thymic carcinoma.

Narrative review of immunotherapy in thymic malignancies

“…The AIDs were presented before (12.6%) and after (6.4%) besides the diagnosis (81%). Concerning histologic subtypes, more than 40% of prevalence were assessed in B2 and B3 subtypes (45% and 41% respectively) (43,44). Thymomas AB, B1 and B2 are rich with lymphocyte agglomerates, suggesting that those tumors are most frequently associated with AIDs than TC and B3 thymomas (45).…”

“…Thymomas AB, B1 and B2 are rich with lymphocyte agglomerates, suggesting that those tumors are most frequently associated with AIDs than TC and B3 thymomas (45). However, several series have found a high prevalence of autoimmune events in thymoma B3 (13,14,43). Importantly, TC are rarely associated with AIDs (41,46).…”

“…Several series have reported no MG in TC (14,47) with a small representation of AIDs overall (44) maybe due to the presence of non-immature T-cells. The high incidence of AIDs in TETs in addition of the presentation of autoimmune symptoms afterward diagnosis of cancer (43,44) requires an extremely close monitoring during treatment with ICI.…”

“…Antibodies against the AchR are essential for the development of MG, as explained above, but also MuSK and Lrp4 antibodies (85). Interestingly, pure red cell aplasia has been described as the most common AID besides MG (43), however it has not been reported in these trials with ICI.…”

“…Immunotherapy is not evoked in type B1/B2 thymoma due to the high rate of AIDs (13,14,43) and should not be delivered in an off-label setting without full disclosure of risks in the multidisciplinary tumor board. Several clinical trials with ICI alone or in combination are ongoing.…”