Editorial Note:The 66th Annual Meeting of the American Society of Hematology (ASH) was held from December 7–10, 2024, in San Diego, USA. As the largest international academic conference in hematology, it showcased cutting-edge research and the latest advancements in drug development, representing the highest level of academic achievement in the field. Severe aplastic anemia (SAA) remains a challenging condition to treat, with a poor prognosis, making it a focal point for research. At this year's ASH meeting, Dr. Fengkui Zhang and his team from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences presented a study (Abstract 304) exploring the efficacy of combining the novel thrombopoietin receptor agonist (TPO-RA), Hetrombopag, with immunosuppressive therapy (IST) for treating SAA. The study demonstrated promising results. In an exclusive interview, Hematology Frontier delved into the findings and implications of this research with Professor Zhang. Below is a detailed summary and analysis of the study and interview.- Study Highlights
Hetrombopag Combined with Immunosuppressive Therapy (IST) in the First-Line Treatment of Severe Aplastic Anemia: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial
Abstract 304
Hematology Frontier: Hematopoietic stem cell transplantation (HSCT) is a key treatment for SAA. For patients unable to undergo transplantation, immunosuppressive therapy (IST) is the mainstay. Could you discuss the overall efficacy and prognosis for this subset of SAA patients?
- Dr. Fengkui Zhang:
Hematopoietic stem cell transplantation (HSCT) is the preferred treatment for SAA. However, many patients lack a suitable donor and must rely on immunosuppressive therapy (IST). Over the past 20–30 years, IST has seen significant advancements, particularly with the introduction of thrombopoietin receptor agonists (TPO-RAs), which have markedly improved response rates and the quality of hematological remission. The time to achieve a hematological response has also shortened significantly. Nearly 80% of patients achieve a hematological response, and many can enjoy long-term survival.
In China, we have developed innovative TPO-RAs. At this year’s ASH meeting, our prospective, double-blind, randomized controlled clinical trial demonstrated that adding Hetrombopag to IST significantly enhanced hematological response rates. This finding underscores the therapeutic potential of TPO-RAs in improving outcomes for SAA patients unable to undergo transplantation.
Hematology Frontier: Combining IST with TPO-RA is the first-line treatment for SAA patients unable to undergo transplantation. Could you elaborate on recent advances in this area?
- Dr. Fengkui Zhang:
This field has seen considerable progress in recent years. After Eltrombopag demonstrated efficacy in treating refractory aplastic anemia, hematologists quickly extended its use to first-line treatment for aplastic anemia (AA).
At the National Institutes of Health (NIH), a prospective cohort study achieved remarkable results in first-line AA treatment. Similarly, a multicenter, prospective, randomized controlled trial conducted in Europe demonstrated that adding TPO-RAs to IST enables AA patients to achieve faster and better hematological remission.
Our study adopted a similar design—prospective, double-blind, and randomized controlled—and yielded positive results with TPO-RA combined with IST. Notably, research presented at this ASH meeting suggests that longer-term TPO-RA use can further benefit AA patients. For example, the European Bone Marrow Transplantation Registry (EBMT) reported a prospective controlled study where Eltrombopag was used for up to 24 months, showing positive outcomes. This has bolstered our confidence in the long-term application of TPO-RAs.
Hematology Frontier: How would you evaluate the efficacy and safety of the novel TPO-RA Hetrombopag in treating SAA?
- Dr. Fengkui Zhang:
Our study utilized Hetrombopag, a TPO-RA developed in China. Its molecular structure is highly similar to Eltrombopag, but with modifications to the molecular terminals to enhance its affinity for TPO receptors, thereby improving pharmacodynamics. Additionally, Hetrombopag replaces biphenyl groups with heterocyclic carboxyl groups, reducing hepatotoxicity and improving safety.
Overall, Hetrombopag demonstrated comparable or even superior efficacy and safety compared to Eltrombopag. While there are no head-to-head studies comparing the two agents, data from our Phase I–III clinical trials suggest Hetrombopag offers significant benefits.
Hematology Frontier: Could you summarize the key advances in treating severe and refractory aplastic anemia presented at this year’s ASH meeting?
- Dr. Fengkui Zhang:
Despite recent progress in treating SAA, a subset of patients remains poorly responsive to current therapies. At this ASH meeting, a British team reported promising results from a study using transfusions of ex vivo-expanded regulatory T lymphocytes in SAA treatment. This innovative approach may represent a novel and effective strategy beyond IST combined with TPO-RAs. We eagerly anticipate these new therapies delivering real clinical benefits to patients.
About Dr. Fengkui Zhang
Institution: Blood Diseases Hospital, Chinese Academy of Medical Sciences
Title: PhD, Professor, Chief Physician, and Doctoral Supervisor
Expertise: Clinical and experimental research on hematopoietic and red blood cell disorders
Professor Zhang has made pioneering contributions in several areas, including reporting on large granular lymphocyte leukemia, congenital dyserythropoietic anemia, hematopoietic instability in aplastic anemia, and first-line IST protocols using ATG and CsA combined with high-dose cyclophosphamide.
He serves as the Deputy Editor of Chinese Journal of Hematology and is on the editorial boards of multiple hematology journals. With over 90 published papers, Professor Zhang has led numerous research projects and has been recognized as an outstanding healthcare worker, an exemplary Communist Party member, and a recipient of the Tianjin May 1st Labor Medal.
