Table 1.

Previous and ongoing landmark trials evaluating eltrombopag as a single agent or in combination in SAA and MAA as first- or second-line therapy.

Study (institution/country)	Indication	N	Eltrombopag dose (duration)	Treatment regimen	Response rate
First-line therapy
Phase I/II, single-arm, open- label, nonrandomized, prospective study of eltrombopag + horse ATG + CSA. (NCT01623167) NIH/USA	SAA/vSAA	Cohort 1: 30 Cohort 2: 31 Cohort 3: 31	150 mg/day	Eltrombopag/ATG/CSA	Overall response (CR + PR) at 6 months: Cohort 1: 80% Cohort 2: 87% Cohort 3: 94%
Phase III, horse ATG + CSA + eltrombopag; prospective, randomized, open label (RACE). (NCT02099747) Europe	SAA/vSAA	197	150 mg/day day 14 until 6 months (or 3 months if CR)	Eltrombopag/ATG/CSA	CR response at 3 months: 76%
Phase II, eltrombopag for moderate AA. (NCT01328587) NIH/USA	MAA, unilineage cytopenia	34	Dose escalation from 50 mg to 300 mg for 16–20 weeks	Eltrombopag	Hematologic response* at 16–20 weeks: 50%
Efficacy and safety of eltrombopag in combination with CSA in moderate AA: prospective, randomized, multicenter study. (NCT02773225) Europe	MAA	–	150 mg/day until 12 months (or stopped after 6 months if not in PR/CR)	Eltrombopag/CSA	Ongoing
Second-line therapy
Phase II, eltrombopag; nonrandomized, single arm, open label. (NCT00922883) NIH	AA refractory to standard IST	25	Dose escalation from 50 mg/day to 150 mg/day for a total of 12 weeks	Eltrombopag	Hematologic response$ at 12 weeks: 44%
Phase II, eltrombopag; nonrandomized, single arm, open label. Extended fixed dosing (150 mg) in SAA. (NCT01891994) NIH	rSAA/vSAA	39	150 mg/day for 6 months (possible to continue if response)	Eltrombopag	Hematologic response$ at 3–4 months: 49%

^*Hematologic response in patients eligible for a platelet response was defined as an increase in platelets of >20 × 10⁹/L from baseline platelet nadirs and transfusion independence; for patients eligible for a RBC response, an increase in hemoglobin of >15 g/L from baseline for those not transfusion dependent, or a reduction of RBC transfusions by >50% over an 8-week period compared with the 8 weeks before study entry for transfusion-dependent patients. As all patients had an ANC >0.5 × 10⁹/L at study entry and were therefore not at risk for serious infections related to neutropenia, increases in ANC were not considered for response assessment.

^$Hematologic response was defined as uni- or multilineage recovery by one or more of the following criteria: (a) platelet response (increase to 20 × 10³/ml above baseline or stable platelet counts with transfusion independence for a minimum of 8 weeks in those who were transfusion dependent on entry into the protocol); (b) erythroid response (when pretreatment hemoglobin was 90 g/L, defined as an increase in hemoglobin by 15 g/L or, in transfused patients, a reduction in the units of packed RBC transfusions by an absolute number of at least four transfusions for 8 consecutive weeks, compared with the pretreatment transfusion number in the previous 8 weeks); (c) neutrophil response (when pretreatment ANC of 0.5 × 10³/ml as at least a 100% increase in ANC, or an ANC increase 0.5 × 10³/ml, and the toxicity profile as measured using Common Terminology Criteria for Adverse Events).

AA, aplastic anemia; ANC, absolute neutrophil count; ATG, antithymocyte globulin; CR, complete response; CSA, cyclosporine; IST, immunosuppression therapy; MAA, moderate aplastic anemia; NIH, National Institute of Health; PR, partial response; RBC, red blood cell; SAA, severe aplastic anemia; rSAA, refractory severe aplastic anemia; vSAA, very severe aplastic anemia.