Severe aplastic anemia used to have few options and mortality was high, but a new class of drugs offers some hope.
A recent review examined treatment options for aplastic anemia (AA), a hematopoietic stem cell disorder marked by pancytopenia and hypocellular bone marrow.
The degree of pancytopenia (when all 3 types of blood cells have low counts) determines the severity of AA, which has high mortality in the worst forms of the disease.
Although different causes of AA may be considered, such as environmental or genetic, most cases of AA are immune-mediated.
For a few decades, hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) have changed AA outcomes by improving marrow function and pancytopenia.
Outcomes with either HSCT or IST are similar, and the choice depends on patient age, availability of a histocompatible donor, comorbidities, and patient preference.
Allogeneic HSCT is generally preferred in patients younger than 40, while IST is typically seen in patients older than 40.
While standard IST produces a hematologic response rate of 60% to 70%, about one-third of patients eventually relapse, and 10% to 15% can develop cytogenetic abnormalities.
The introduction of eltrombopag, a thrombopoietin receptor agonist, improved severe AA outcomes as both second-line and first-line therapy combined with IST.
Eltrombopag, initially approved in 2008, received FDA breakthrough treatment designation in 2014 for patients with aplastic anemia for which immunosuppression has not been successful and was approved for that indication in 2018
As a single agent, eltrombopag in doses up to 150 mg daily improved cytopenias in 40% to 50% in those who failed initial IST.
Combined with IST as upfront therapy, eltrombopag achieved an overall response of about 90% and complete responses of about 50%, higher than observed with IST alone (about 65% and 10%, respectively).
The majority of patients were alive after a median follow-up of 18 months.
The action of eltrombopag continues to be confirmed in other studies involving longer follow-up times and real-word data in different combinations and doses. In addition, understanding which patients would benefit from eltrombopag through biomarkers would be useful.
Another thrombopoietin receptor agonist in AA, romiplostim, is performing similarly, suggesting a class effect, and the author said more discoveries about how these drugs can be optimized are expected.
Scheinberg P. Novel therapeutic choices in immune aplastic anemia.F1000Res. Published online September 10, 2020. doi: 10.12688/f1000research.22214.1