Abstract Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical
Background: The therapeutic approach for transfusion-dependent non-severe aplastic anemia (TD-NSAA) is undetermined. Though the British guideline recommended intensive immunosuppressive therapy as the first line therapy for TD-NSAA, the cost and risk were relatively high. Hetrombopag, a thrombopoietin receptor agonist (TPORA), has shown encouraging results in severe aplastic anemia, but its efficacy has not been investigated in TD-NSAA.
Aims: This study aimed to investigate the efficacy of hetrombopag plus cyclosporine A (CsA) for TD-NSAA.
Methods: Hetrombopag was taken at an initial dose of 7.5 mg per day to a maximum of 15 mg per day. CsA was basically initiated at 3~5 mg/kg daily and then adjusted according to the response or side effects, to maintain the target concentration between 150 and 250 μg/L. The primary endpoint was hematologic response in ≥ 1 lineage.
Results: 19 eligible patients who were enrolled and received hetrombopag plus CsA from September 2021 to February 2023 were collected by prospective registration in the Chinese Eastern Collaboration Group of Anemia (ChiCTR2100045895) (Table 1). The median follow-up period was 8.2 [0.8~16.8] months. 14 of the 19 patients (74%) responded in ≥ 1 lineage, including 13 patients (68%) achieving partial response and one patient (5%) achieving complete response. The median time to initial hematologic response was 6.1 [1.7~28.4] weeks. 9 of 15 patients (60%) achieved erythroid response; 13 of 19 patients (68%) achieved platelet response and 11 of 14 patients (79%) achieved neutrophil response. The median time to erythroid, platelet and neutrophil response were 15, 8.3 and 19.7 weeks, respectively. The survival rate was 95%, with one patient died of intracerebral hemorrhage 9 months after initiation of hetrombopag. Drug-induced hepatic or renal injury happened in 4 patients (21%); all showed remission after dose reduction or discontinuation.
Summary/Conclusion: The combination of hetrombopag with CsA is an effective regimen in patients with TD-NSAA.
Table 1 Baseline Clinical Characteristics of Patients
| Characteristic | |
|---|---|
| Follow-up — months | 8.2 [Range: 0.8~16.8] |
| Age — yrs | 50 [Range: 18-67] |
| Age category — no. (%) | |
| <40 | 6 (32) |
| ≧40 | 13 (68) |
| Sex — no. (%) | |
| Female | 10 (53) |
| Male | 9 (47) |
| Transfusion dependence category — no. (%) | |
| RBC dependent | 15 (79) |
| Platelet dependent | 19 (100) |
| Laboratory values | |
| Hemoglobin — g/L | 85 [IQR: 67-101] |
| Neutrophil count — per μL | 1030 [IQR:818-1600] |
| Lymphocyte count — per μL | 1675 [IQR: 1105-2365] |
| Platelet count — per μL | 20500 [IQR: 10000-33750] |
| Reticulocyte count — per μL | 54700 [IQR: 34400-71000] |
| RDW-CV % | 14.5 [IQR: 13.3-18.9] |
Keywords: Aplastic anemia, Thrombopoietin (TPO)