Real-world outcomes of eltrombopag-containing regimens as frontline treatment for aplastic anemia: A multi-center retrospective study

Abstract Background Eltrombopag (EPAG), an oral thrombopoietin receptor agonist, has emerged as a promising frontline treatment for aplastic anemia (AA). It improves the overall response rate and shortens the time to response with a favorable safety profile. Combined with immunosuppressive therapy, EPAG has become a standard first-line treatment. However, real-world data on its efficacy and long-term outcomes are limited. This study represents one of the largest real-world datasets to date on long-term outcomes of Asian AA patients treated with EPAG-based regimens. Methods A multi-center retrospective study of adult patients with therapy-naïve acquired AA treated with EPAG-containing regimens in 7 hospitals in Hong Kong over a 10.5-year period (January 2014 to July 2024) was conducted. The Camitta criteria[1] for defining disease severity were adopted. Hematologic response, failure-free survival (FFS), and overall survival (OS) were evaluated. Partial response (PR) was defined as recovery of blood parameters above and beyond MAA/SAA, and complete response (CR) was defined by neutrophil count ≥1.0 x 109/L, platelet count ≥100 x 109/L, and hemoglobin ≥10 g/dL. Overall response (OR) was the composite of PR and CR. The outcome was correlated with clinicopathologic characteristics, including disease severity, EPAG dosing, and time to treatment initiation. Results There were 118 patients (44 men and 74 women) with AA (moderate, MAA, N=18; severe, SAA, N=66; very severe, vSAA, N=34), at a median age of 57 (18-87) years. A paroxysmal nocturnal hemoglobinuria clone was detected in 40% of patients with available information (N=107). Treatment regimens included EPAG (N=8), EPAG+cyclosporin A (CsA) (N=58) and EPAG+CsA+antithymocyte globulin (ATG) (N=52). For MAA patients, most were treated with EPAG+CsA (N=14). The OR rate was 93% (CR, N=57%; PR, N=36%). At a median follow-up of 67 (5-121) months, the 5-year FFS and OS were 65% and 80% respectively. For SAA/vSAA, most were treated with EPAG+CsA (N=44) and EPAG+CsA+ATG (N=50). The OR was 66% (CR, N=48%; PR, N=18%). At a median follow up of 57 (1-132) months, The 5-year FFS and OS were 70% (95% confidence interval, CI: 58-84%) and 67% (95% CI: 57-78%). EPAG+CsA+ATG, compared with EPAG+CsA, resulted in higher CR (60% versus 34%, P=0.014); higher OR (76% versus 52%, P=0.019); shorter time to CR (6.5 versus 11.2 months, P=0.011); comparable time to first response (2.7 versus 2.6 months, P=0.2); comparable 5-year FFS (78% versus 58%, P=0.2); and superior 5-year OS (not reached versus 5.5 years, P=0.0006). 5 patients received allogeneic haematopoietic stem cell transplantation (HSCT) at partial response (N=1), or due to no response (N=2) or relapse (N=2). For SAA/vSAA, delay in treatment (time from diagnosis to treatment initiation ≥25 days) was associated with inferior OS (Hazard ratio, HR 2.37, P=0.03). For patients achieving CR, the OS was >90% at 7 years. Multivariate analyses showed inferior OS to be associated with age at diagnosis >65 years (HR 7.0, P=0.03); achieving PR only (HR 8.6, P=0.01); and no response to treatment (HR 24, P<0.001). As a lower EPAG dose is recommended for Asian patients, the dosage of EPAG used and its impact were investigated. The median duration of treatment with EPAG-containing regimen was 25 months. The dosage of EPAG ranged from 25 mg to 200 mg daily. The mean daily dose of EPAG in the first month of treatment was 50 mg and 75 mg in 36% and 29% of patients respectively. There was no dose-dependent improvement of CR or OR observed in MAA/SAA/vSAA patients. Conclusions EPAG-containing regimens, particularly EPAG+CsA+ATG, demonstrated high efficacy in treatment-naïve AA patients. Achieving CR predicted superior survival outcomes. Early treatment initiation might benefit AA patients. These findings highlight the need for prospective trials to optimise EPAG-based strategies. Finally, prospective comparison with frontline allogeneic HSCT is also warranted. Reference Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, Hillmen P, Ireland R, Kulasekararaj A, Mufti G et al: Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol 2016, 172(2):187-207.