Fixed-cycle oral pomalidomide/lenalidomide-based therapy is associated with durable treatment-free remission in idiopathic multicentric castleman disease with TAFRO syndrome: a single-center retrospective study

Abstract Background Idiopathic multicentric Castleman disease with TAFRO syndrome (iMCD-TAFRO) is a rare and severe subtype of iMCD characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. Current treatments often require prolonged or indefinite administration and frequent hospital visits, imposing substantial burdens on patients. We evaluated the clinical outcomes and safety of a fixed-cycle oral immunomodulatory drug (IMiD)-based regimen in patients with iMCD-TAFRO. Methods In this single-center retrospective study, seven patients with iMCD-TAFRO who received an oral immunomodulatory drug (IMiD)-based fixed-cycle regimen were analyzed. Six patients received pomalidomide-dexamethasone or lenalidomide-dexamethasone without concurrent intravenous therapy, whereas one patient received pomalidomide-dexamethasone plus concurrent siltuximab as the initial treatment strategy. The primary endpoint was the overall response rate (ORR) at the prespecified 8-week (± 2 weeks) assessment window. Key secondary endpoints included paired changes in C-reactive protein (CRP), albumin, platelet count, and serum creatinine (Scr) from baseline to month 2. Best overall response was analyzed as an exploratory endpoint. Results At the 8-week assessment, four of seven patients achieved a partial response (ORR, 57.1%; 95% CI, 18.4–90.1%), while three had stable disease; no complete responses were observed at this time point. With continued therapy and follow-up, all seven patients achieved complete response as their best overall response (best ORR, 100%; 95% CI, 59.0-100.0%). The median time to initial response was 2.0 months (IQR, 2.0-3.5). Paired analyses from baseline to month 2 demonstrated statistically significant changes in CRP, albumin, and serum creatinine, whereas platelet counts showed numerical improvement without reaching statistical significance. The median treatment duration was 6 months (range, 2–12). Six patients remained in treatment-free remission at last follow-up, with a median treatment-free remission duration of 15.5 months (range, 4–39). One patient relapsed after a prolonged TTNT of 84 months from treatment initiation. Grade 3 adverse events were limited to hyperbilirubinemia ( n  = 1) and febrile neutropenia ( n  = 1); no thromboembolic events or secondary malignancies occurred. Conclusions This fixed-cycle oral IMiD-based regimen, with or without concurrent anti-IL-6 therapy in selected cases, was associated with encouraging clinical and laboratory responses in patients with iMCD-TAFRO, including improvements in inflammatory markers, vascular leak, and renal function. Durable treatment-free remission after a finite course of therapy was observed in most patients in this cohort. Given the retrospective design and limited sample size, these findings should be interpreted cautiously and require confirmation in larger multicenter prospective studies.