N Engl J Med
Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia.
Abstract
Background
A single-group, phase 1-2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia.
Methods
In this prospective, investigator-led, open-label, multicenter, randomized, phase 3 trial, we compared the efficacy and safety of horse ATG plus cyclosporine with or without eltrombopag as front-line therapy in previously untreated patients with severe aplastic anemia. The primary end point was a hematologic complete response at 3 months.
Results
Patients were assigned to receive immunosuppressive therapy (Group A, 101 patients) or immunosuppressive therapy plus eltrombopag (Group B, 96 patients). The percentage of patients who had a complete response at 3 months was 10% in Group A and 22% in Group B (odds ratio, 3.2; 95% confidence interval [CI], 1.3 to 7.8; P = 0.01). At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% in Group A and 68% in Group B. The median times to the first response were 8.8 months (Group A) and 3.0 months (Group B). The incidence of severe adverse events was similar in the two groups. With a median follow-up of 24 months, a karyotypic abnormality that was classified as myelodysplastic syndrome developed in 1 patient (Group A) and 2 patients (Group B); event-free survival was 34% and 46%, respectively. Somatic mutations were detected in 29% (Group A) and 31% (Group Β) of the patients at baseline; these percentages increased to 66% and 55%, respectively, at 6 months, without affecting the hematologic response and 2-year outcome.
Conclusions
The addition of eltrombopag to standard immunosuppressive therapy improved the rate, rapidity, and strength of hematologic response among previously untreated patients with severe aplastic anemia, without additional toxic effects. (Funded by Novartis and others; RACE ClinicalTrials.gov number, NCT02099747; EudraCT number, 2014-000363-40.).
Related Questions
For transplant-ineligible aplastic anemia planned for immunosuppression, how do you approach duration and tapering of cyclosporine and eltrombopag?
One of the most common mistakes in the management of AA is premature tapering of cyclosporine or tacrolimus. If there is a complete remission, and by that I mean normalization of counts, not complete remission as defined in some papers (e.g., ANC 1000, Plts 100,000, Hb 10 as in de Latour et al., PMI...
How do you approach treatment for a patient with hypoplastic MDS who is not eligible for transplant?
I believe it is reasonable to try immunosuppressive therapy particularly if the patient is positive for HLA-DR15. I would treat such a patient with triple immunosuppressive therapy with horse ATG, cyclosporine, and eltrombopag (de Latour et al., PMID 34986284) if they are HLA-DR15 positive. If they ...