Combining avatrombopag with cyclosporine improved platelet levels and improved overall response rates (ORR) and complete response (CR) rates among elderly patients with transfusion-dependent, non-severe aplastic anemia compared to cyclosporine alone. These results from a single-center, retrospective, 52-patient, Chinese study were presented at the European Hematology Association (EHA) 2024 Congress.1
“Adding avatrombopag to cyclosporine therapy achieved a higher ORR and CR and resulted in a faster response than cyclosporine alone,” Moonjung Jung, MD, MS, a hematologist and an assistant professor of medicine, oncology, and genetic medicine at Johns Hopkins University School of Medicine in Baltimore, who was not involved in the study, told ASH Clinical News. “Considering the overall response is about 50% with cyclosporine or eltrombopag as a single agent for moderate aplastic anemia, this combination therapy appears to have achieved a higher response rate.”
Elderly patients with transfusion-dependent, non-severe aplastic anemia have limited therapy options because of transplantation ineligibility and safety concerns owing to comorbidities. The typical treatment choice for these patients is single-agent cyclosporine or a single-agent thrombopoietin (TPO) mimetic, such as eltrombopag or romiplostim, which results in an ORR of about 50%.2,3 Other treatment options include other calcineurin inhibitors, such as tacrolimus, for those who cannot tolerate cyclosporine.
In the current study, researchers analyzed retrospective data from patients aged 60 and older who were newly diagnosed with acquired aplastic anemia and had been treated either with single-agent cyclosporine or the combination of avatrombopag and cyclosporine between September 2020 and July 2023. Twenty-six patients were treated with the combination and 26 with single-agent cyclosporine. The baseline characteristics were similar between the two groups.
“It is a reasonable next step to combine cyclosporine with a TPO mimetic to achieve a higher response rate while monitoring side effect profiles,” Dr. Jung said.
The ORR in the study was 46.2% in the combination-treatment group compared to 15.4% in the cyclosporine monotherapy group (p=0.016) at one month. The ORR in the combination group remained significantly higher throughout the entire study, past six months, compared to the monotherapy group. At the end of follow-up, the ORR was 76.9% in the combination group compared to 50.0% in the monotherapy group (p=0.044).
“Even without intensive immune-suppressive therapy, the ORR at six months was 76.9%, and about half of patients achieved a CR at the end of follow-up with the combination,” Dr. Jung said.
“It is also notable that this higher response rate was achieved in older, presumably less-fit patients without significant added side effects,” Dr. Jung added.
Patients who received the combination therapy had a shorter time to achieve first response (p=0.008) and CR (p=0.010) compared to those who received cyclosporine alone. Patients treated with avatrombopag with cyclosporine exhibited a higher rate of platelet transfusion independence at the third (p=0.011) and sixth month (p=0.011) as well as at the end of follow-up (p=0.045). Patients treated with the combination also had a higher increase in platelet levels at the end of follow-up compared to the monotherapy group (p=0.033).
No differences were observed in side effects or relapse rates between the two groups. There was a trend toward a superior event-free survival in the combination group compared to monotherapy cyclosporine (p=0.101).
The authors noted they did not identify any ORR predictive factors in either patient group.
“However, the caveat is that this study is a retrospective study; therefore, direct comparison to prior prospective studies is inappropriate. Rather, this study provides the rationale for a prospective study comparing this combination to a single agent — either cyclosporine or TPO mimetics,” Dr. Jung said.
“I am particularly interested in whether there were any clonal evolution cases in this study. There is a theoretical concern that TPO mimetics can stimulate the growth of malignant clones. Patients with inherited bone marrow failure syndromes with a higher risk of clonal evolution usually present with moderate aplastic anemia rather than severe aplastic anemia. Therefore, it would be important to follow these patients longer to assess the risk of clonal evolution in both treatment arms,” Dr. Jung explained.
Currently, the authors of the current retrospective analysis are conducting a follow-up prospective single-arm study (NCT06004752) testing the efficacy of this avatrombopag plus cyclosporine combination in elderly patients with non-severe aplastic anemia.4 Another China-based phase II clinical trial is testing the thrombopoietin mimetic herombopag combined with cyclosporine in the same patient population (NCT05660785).
Any conflicts of interest declared by the authors can be found in the original abstract.
References
- Zhang Z, Hu Q, Wang L, et al. Cyclosporine plus avatrombopag versus cyclosporine alone for first-line treatment of elderly patients with transfusion-dependent non-severe aplastic anemia: a single center, retrospective study. Abstract P1919. Presented at the European Hematology Association (EHA) 2024 Congress; June 14, 2024; Madrid, Spain.
- Marsh J, Schrezenmeier H, Marin P, et al. Prospective randomized multicenter study comparing cyclosporin alone versus the combination of antithymocyte globulin and cyclosporin for treatment of patients with nonsevere aplastic anemia: a report from the European Blood and Marrow Transplant (EBMT) Severe Aplastic Anaemia Working Party. Blood. 1999;93(7):2191-2195.
- Fan X, Desmond R, Winkler T, et al. Eltrombopag for patients with moderate aplastic anemia or uni-lineage cytopenias. Blood Adv. 2020;4(8):1700-1710.
- Zhang T, He G, Shi J. P763: Efficacy and safety of avatrombopag in the treatment of transfusion-dependent non-severe aplastic anemia. HemaSphere. 2023;7(S3):e74779bf.
