1901P Immunomodulatory role of multi-agent therapy in thymic epithelial tumours and severe immunological dysregulation

Abstract

The association of different parathymic entities is common in thymic epithelial tumors (TETs), although only anecdotal case reports of TET patients exhibiting both pure red cell aplasia (PRCA) and Good Syndrome (GS) were described to date. We prospectively evaluated the outcomes of TET patients with PRCA and GS treated with combination therapy allowing prolonged control of TET, autoimmunity (PRCA) and immunodeficiency (GS). From 2013 consecutive TET patients, treated at Rare Tumors Reference Center of University Federico II, underwent diagnostic work-up for GS and PRCA, in the presence of suspicious symptoms. Subjects with GS who developed also PRCA were treated with a multi-agent therapy, including long acting octreotide 30 mg i.m. every 4 weeks, prednisone 0.6-1 mg/kg/daily (tapered when reaching Hb > 13 g/dl), cyclosporine escalation dose 50 to 200 mg/daily, darbepoietin 150 mcg weekly, intravenous immunoglobulin at 500 mg/kg per day for 5 days/monthly (tapered to 30 gr every 4 weeks), cotrimoxazolo antibiotic prophylaxis. Reticulocytes, serum immunoglobulin, C reactive protein (CRP), and Hb levels were closely monitored. Immunophenotype was assessed on whole blood by 8-colour immunophenotyping kit and Treg detection kit (CD4/CD25/CD127). TET Time to progression (TET-TTP), PRCA remission (PRCA-R), as well as occurrence of life treating infections, were assessed. 16 patients were included in this study. Median age was 44 years (range 33-65); male/female ratio was 1/1; the most frequent histotype was B2 thymoma (57%). Prolonged PRCA-R was observed in all but one patient, with median time to PRCA-R of 40 days. Correlation between increase of reticulocytes and circulating Treg was detected (p = 0.0003). At the time of the last follow-up, 15 patients were alive; 2 had PRCA recurrence after a median of 2 years from the initial diagnosis, one patient died for fatal medullary aplasia and 2 were hospitalized for staphylococcus pneumonitis. Median TET-TTP of 11 months was registered. This is the largest series of TET patients with PRCA and GS ever reported. The proposed multi-agent therapy achieved fast and prolonged PRCA-R, prolonged TET control and low rate of life treating infectious complications.