Clinical characteristics, treatment strategies, and response patterns in evans syndrome: Initial analysis from the spanish resti cohort Free

Introduction: Evans syndrome (ES) is a rare, heterogeneous autoimmune disorder characterized by the simultaneous or sequential occurrence of autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and/or autoimmune neutropenia (AIN). Although historically considered idiopathic, ES may also occur in association with systemic autoimmune diseases, lymphoproliferative disorders, or immunodeficiencies. Given its low prevalence and diverse presentation, evidence-based guidelines for management remain limited, particularly in adult populations. Most available data derive from pediatric cohorts or small retrospective series, and therapeutic decisions are often extrapolated from the management of isolated ITP or AIHA.

Objective: To describe the clinical features, treatment modalities, and hematologic responses in a Spanish cohort of patients with ES enrolled in the national ITP registry (RESTI).

Methods: This is a retrospective multicenter study based on data from the RESTI. We included patients with ES, defined by the coexistence (simultaneous or sequential within 10 years) of ITP and AIHA and/or AIN Diagnoses were based on established international criteria. Data on demographics, clinical presentation, treatments, and responses were collected using a standardized form. Treatment responses were defined according to hematologic response criteria for each cytopenia as response(R), complete response (CR), no response (NR) y corticosteroid dependence SD). Categorical variables were expressed as relative frequencies and quantitative variables as median and interquartile range (IQR) or median and range. The study was approved by the institutional review board and conducted in accordance with the Declaration of Helsinki.

Results: A total of 44 patients were included, with a median age of 25.5 years (IQR: 8.25–57.25), 50% were female. Seventeen patients were younger than 18 years old, with median age of 8 years (IQR: 1–10) and 27 adult patients (median age 49 years old, IQR: 30–68 years). All patients presented ITP, 65.9% had AIHA (n=29), and 56.8% had AIN (n=25). The median follow-up was 306 weeks (IQR: 128–575).

All patients received corticosteroids as first-line therapy, with a median duration of 90 days (range: 4–1350). Median time to response in ITP was 20 days, and to complete response (CR) was 68 days. AIHA showed a median response time of 13 days, while neutropenia responded in a median of 3 days. For ITP, response rates were 20.5% R, 50% CR, 20.5% CD, and 9% no response (NR). For AIHA: 9.1% PR, 29.5% CR, 9.1% CD, and 9.1% NR. Neutropenia had a response rate of 76%.

Second-line treatments included rituximab in 10 patients (375 mg/m²/week; four cycles. Among them, ITP responses included 40% CR, 20% R, and 40% NR. In AIHA (n=8), 50% achieved CR. Among two patients with neutropenia, one responded. Cyclosporine was used in two patients with dual-lineage cytopenias, resulting in AIHA response in 41 days and neutrophil recovery in 15 days.

Fostamatinib was used in four patients with concurrent ITP and AIHA. Median baseline platelets were 14 ×10⁹/L and hemoglobin 9.8 g/dL. The median time from diagnosis to fostamatinib initiation was 531 days. All patients were on concomitant therapy (corticosteroids or avatrombopag). Median time to ITP response was 15.5 days; CR was achieved at 38.5 days. For AIHA, response and CR were achieved at 45 and 83 days, respectively. All patients reached CR in both ITP and AIHA without toxicity. In two patients, fostamatinib was successfully discontinued without relapse. At last follow-up, median platelet count was 158 ×10⁹/L, hemoglobin 134 g/L, and neutrophil count 5.2x10e9/L

Thrombopoietin receptor agonists (TPO-RAs) were used in five patients with ITP, but showed no efficacy in AIHA and were not used for neutropenia.

Conclusion: This analysis from RESTI highlights the clinical heterogeneity and treatment challenges in Evans syndrome. Corticosteroids remain first line of therapy but theyt are associated with incomplete or transient responses in many patients. Rituximab demonstrated moderate efficacy across lineages, while fostamatinib showed rapid, durable responses in both ITP and AIHA without observed toxicity, even allowing treatment withdrawal in some cases. The lack of response to TPO-RAs in AIHA underscores the need for lineage-specific therapeutic strategies. These findings support the use of registry data to inform clinical decision-making of this rare autoimmune condition.