Sirolimus for refractory/relapsed warm autoimmune hemolytic anemia and Evans syndrome: a prospective study.

abstractEffective therapeutic options remain limited for adults with relapsed or refractory (R/R) warm autoimmune hemolytic anemia (wAIHA) and Evans syndrome (ES). We conducted a prospective, single-center, open-label clinical trial to evaluate the efficacy and safety of sirolimus. Adult patients with R/R wAIHA or ES and hemoglobin levels <100 g/L received oral sirolimus (1-3 mg/day; target trough concentration, 4-15 ng/mL) for ≥6 months. The coprimary end points were overall response rate (ORR) and complete response rate (CRR) at 6 months; secondary end points included 12-month efficacy, safety, and relapse rates. Seventy-eight consecutive patients were enrolled (median age, 52 years [interquartile range (IQR), 38-65]), including 63 (80.8%) with wAIHA and 15 (19.2%) with ES. With a median follow-up of 13.9 months (IQR, 12.7-17.0), sirolimus achieved a 6-month ORR of 80.7% (81.0% for wAIHA and 80.0% for ES) and CRR of 51.3% (52.4% for wAIHA and 46.7% for ES). Median times to overall and complete response were 2.4 months (IQR, 1.8-5.0) and 3.6 months (IQR, 2.3-7.0), respectively. Responses were sustained at 12 months (ORR, 78.2%; CRR, 50.0%). Treatment-emergent adverse events occurred in 28.2% of patients and were predominantly mild and reversible. Relapse and mortality rates were 12.7% and 2.8%, respectively. No baseline clinical characteristics were independently associated with response at 6 months. Sirolimus demonstrated clinically meaningful efficacy, durable responses, and a favorable safety profile, supporting its role as a steroid-sparing option for steroid-dependent patients and a potential treatment alternative for steroid-refractory R/R wAIHA and ES. This trial was registered at www.clinicaltrials.gov as #NCT05925023.