Editor’s Note: From June 8th to 11th, 2023, the 28th European Hematology Association (EHA) Congress was held in Frankfurt, Germany. During this conference, Dr. Hou Ming’s team at Qilu Hospital, Shandong University, China, presented the research findings on the use of the BTK inhibitor ibrutinib for primary immune thrombocytopenia (ITP) (abstract S299). To gain deeper insights into this study and its implications for the current status of ITP treatment, Oncology Frontier had an exclusive interview with Dr. Hou Ming. He provided a detailed overview of the current situation of ITP treatment in China and the promising future of using BTK inhibitors for ITP therapy.
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Incidence and Treatment Status of Primary Immune Thrombocytopenia (ITP) in China
Dr. Hou Ming: Presently, large-scale epidemiological investigations regarding ITP haven’t been conducted in China, resulting in an absence of precise incidence rates specific to China. The estimated incidence ranges from 5 to 10 cases per 100,000 individuals, signifying a substantial accumulation of patients due to ITP’s chronic nature, necessitating long-term management.
With the continual updating and widespread adoption of the “Chinese Guidelines for the Diagnosis and Treatment of Adult Primary Immune Thrombocytopenia,” ITP treatment in China has become more standardized. This guideline not only incorporates the essence of foreign guidelines but also integrates recent domestic prospective multicenter randomized study outcomes. In primary treatment, high-dose oral dexamethasone exhibits rapid efficacy, high complete response rates, minimal long-term adverse effects, good patient tolerance, and cost-effectiveness, becoming the preferred initial treatment. Additionally, conventional-dose prednisone, having efficacy comparable to high-dose dexamethasone, poses challenges in tapering and requires a longer duration, occasionally leading to adverse reactions. Intravenous immunoglobulin (IVIG) therapy, although effective, is expensive and provides transient relief, more suited for critically ill patients or those intolerant to steroids. Anti-D serum is currently unavailable in China. Considering these factors, steroids, particularly high-dose oral dexamethasone, remain the primary choice for initial ITP treatment in China, while IVIG is reserved for severe cases or steroid intolerance.
In subsequent treatments, evidence-based medicine robustly supports recombinant human thrombopoietin (TPO) and TPO receptor agonists, such as eltrombopag, avatrombopag, and romiplostim, as preferred options. These medications have therapeutic indications for ITP treatment and are accessible in China, making them the primary choices for secondary treatment. Additionally, rituximab, fostamatinib, among others, are considered secondary treatment alternatives.
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Irreversible BTK Inhibitor Ibrutinib in ITP Therapy
Dr. Hou Ming: At the EHA Congress, we reported a study on the use of the irreversible BTK inhibitor ibrutinib in treating ITP patients. This Phase II study was led by Qilu Hospital, Shandong University, and involved multiple domestic medical centers, employing the novel BTK inhibitor ibrutinib for ITP therapy. Currently, ITP treatment encounters a bottleneck; initial steroid therapy exhibits a high initial response rate, but upon steroid tapering, relapses are common, resulting in a low sustained remission rate. To address this limitation, we explore two avenues: developing new drugs or repurposing existing ones and combining drugs with different mechanisms. BTK inhibitors reduce or inhibit B lymphocyte activation and proliferation by inhibiting Bruton’s tyrosine kinase, thereby decreasing antibody production. This mechanism holds significant promise for ITP, an autoimmune disease predominantly driven by humoral immunity.
Similar studies have been conducted overseas using a drug called Rilzabrutinib. Results from a Phase II study published in the NEJM in 2022 were highly encouraging, showing an effective rate of 40% in ITP patients previously unresponsive to multiple lines of treatment. Coupled with good tolerance, its future application is highly anticipated. The Phase II study we presented on ibrutinib showed an effective rate of 36.1%, closely resembling the efficacy in patients responding to prior steroid or IVIG treatments, reaching up to 40%. The overall sustained effectiveness is close to 30%, reaching 83% in initially responsive patients at a dosage of 50mg/day, demonstrating good tolerability and safety. Currently, the Phase II study of ibrutinib has concluded, and the initiation of Phase III studies is underway. With China’s vast patient population and researchers’ enthusiasm and confidence, we aim to catch up with the progress of Rilzabrutinib.
TAG: EHA 2023, Interview, Voice of China，Hematological Malignancy, ITP
