Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder caused by acquired gene mutations in hematopoietic stem cells, with complement-mediated intravascular hemolysis being its main pathological feature. The disease is prone to relapse, and its complications severely impact patients’ daily lives, significantly reducing their quality of life. Early treatment is crucial for PNH patients. The 15th Experimental Hematology Conference and the First Rare Blood Disease Academic Conference, hosted by the Chinese Medical Association, was grandly held in Suzhou from March 23 to 24, 2024. Renowned experts and scholars in the field of hematology from home and abroad gathered to share the latest research findings and discuss industry trends. At the conference, Professor Bing Han from Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, gave a wonderful presentation on “New Technologies for the Diagnosis and Treatment of PNH.” Following the conference, Oncology Frontier – Hematology Frontier invited Professor Bing Han to further discuss the diagnosis and treatment methods for PNH, the main challenges faced, and the current survival status of patients.
Oncology Frontier – Hematology Frontier: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease, and its diagnosis and treatment face many challenges. Could you first introduce the current diagnostic and treatment methods for PNH?
Professor Bing Han: Firstly, the clinical manifestations of paroxysmal nocturnal hemoglobinuria (PNH) are diverse. The most common clinical manifestations are hemoglobinuria and anemia, along with some rare clinical manifestations, such as the formation of blood clots in very specific locations (such as the hepatic vein [Budd-Chiari syndrome], other intra-abdominal veins [portal vein, splenic vein, etc.], sinus, skin veins), or ischemic anemia, and initial symptoms may be nonspecific. Therefore, the diagnosis of PNH is very challenging. Fortunately, compared with other bone marrow failure diseases, PNH has its own biomarkers. The development of clone detection and flow cytometry has made clone detection a routine test. The commonly used methods include detecting hemoglobinuria, the presence of the glycosylphosphatidylinositol (GPI)-anchored protein (Flaer) on leukocytes, and clonal markers such as CD55 and CD59. Peripheral blood testing easily achieves the diagnosis of PNH. However, many clinical doctors still miss the diagnosis of PNH. We have seen cases where patients undergo stent placement for recurrent portal vein thrombosis, but clinical doctors did not consider PNH, and the diagnosis of PNH was missed for a long time. Therefore, for PNH, clinical doctors still face significant challenges in diagnosis, mainly due to insufficient recognition of rare diseases. Although there are diagnostic methods for PNH, many non-specialized hospitals and non-hematologists are still unaware of the diagnostic and treatment methods, which is a major challenge we face now.
Oncology Frontier – Hematology Frontier: Last year, China’s first “White Paper on the Survival Status of Chinese Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients” was released. Could you talk about the current survival status of PNH patients in China under existing diagnostic and treatment methods?
Professor Bing Han: The development of PNH in China can be divided into two stages. The first stage is the stage lacking effective drug treatment. In fact, the complement inhibitor for treating PNH, eculizumab, was approved in the United States as early as 2007, but it was not officially launched in China until the end of 2022. Before that, Chinese PNH patients faced enormous difficulties due to the lack of effective drug treatment, so conventional symptomatic supportive treatment had very limited improvement on patients’ prognosis and quality of life. Data from the 2023 “White Paper on the Survival Status of Chinese PNH Patients” showed that the quality of life of many patients was far below that of the healthy population after diagnosis or onset of the disease, and there was a significant difference in survival compared with the normal control group. Statistics show that the 5-year mortality rate of patients is as high as 30%, and the 10-year survival rate is around 70%, indicating significant unmet clinical needs for Chinese PNH patients. After 2022, the first complement inhibitor, recombinant humanized anti-complement protein C5 monoclonal antibody (eculizumab), was officially launched in China, but the price is relatively high, and many families cannot afford it, so the number of patients who can use eculizumab is very limited.
The second stage is the beginning of 2024, when eculizumab was officially included in the national medical insurance, and more and more PNH patients can receive eculizumab treatment. In February of this year, the new generation complement inhibitor, ravulizumab, was approved in China, marking its first approval in all countries worldwide. Following closely, another complement system inhibitor, a specific complement B factor inhibitor, may be launched in China in April. With more and more drugs being launched in China, the accessibility of drugs will greatly increase. At the same time, there are still many innovative complement inhibitors under research and development in China, and some patients may have the opportunity to participate in clinical trials. This is a great opportunity for the diagnosis of PNH.
Oncology Frontier – Hematology Frontier: At this conference, you gave a presentation titled “New Technologies for the Diagnosis and Treatment of PNH.” Could you discuss how these new technologies will help improve the survival of PNH patients?
Professor Bing Han: Before the launch of complement inhibitors, the natural course of PNH patients was very poor. Although PNH is a benign disease, the mortality rate is very high, and even for patients who do not die, their quality of life is very poor due to various complications, so the threat of PNH to patients is no less than that of malignant tumors. However, after the launch of complement inhibitors, statistics show that after 10 years of long-term practice, the survival quality and survival period of patients using eculizumab are almost the same as those of normal people. Now we have more new drugs, such as the newly launched ravulizumab, which is a subcutaneous injection drug, an improvement over eculizumab, which requires intravenous injection every two weeks. The complement B factor inhibitor about to be launched is a more convenient oral drug. In terms of efficacy, the new drugs have to some extent overcome some of the shortcomings of previous drugs, such as extravascular hemolysis, breakthrough hemolysis, C5 polymorphism, and so on, and the efficacy has been improved. We recently conducted a clinical trial on an innovative target that simultaneously inhibits the upstream and downstream pathways, and the preliminary results of the study are quite promising.
With the emergence of more and more new drugs, the efficacy of PNH treatment is getting better, safety is guaranteed, and convenience is increasing—from intravenous to subcutaneous injection, and then to oral administration, with longer intervals between doses, etc. These conveniences will improve treatment compliance and efficacy. Therefore, we also believe that for such a rare disease, from feeling helpless about its adverse outcomes in the past to now actively intervening, and being able to make patients’ lives no different from normal people’s, and returning to normal life, this is also the greatest comfort as a doctor.
Expert Profile
Professor Bing Han
Chief Physician and Professor, Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
Leader of the Red Blood Cell Disease Group, Department of Hematology, Peking Union Medical College Hospital
Core Member of the International Paroxysmal Nocturnal Hemoglobinuria Interest Group (IPIG)
Deputy Director of the Red Blood Cell Disease Group, Hematology Branch, Chinese Medical Association
Leader of the PNH Group, Rare Disease Group, Hematology Branch, Chinese Medical Association
Vice Chairman of the Red Blood Cell Disease Academic Committee, Second Committee of the Geriatrics Branch, Chinese Medical Association
Vice Chairman of the MDS and MPN Working Group, Second Committee of the Hematologic Oncology Branch, Chinese Anticancer Association
Vice Leader of the MDS Disease Group, Chinese Medical Women’s Association
Vice Chairman of the Red Blood Cell Committee, Beijing Cancer Prevention and Control Society
Vice Chairman of the Hematologic Diagnosis Committee, Cell Morphology Professional Committee, Bai Qiu’en Spirit Research Association
Deputy Director of the Red Blood Cell Disease Diagnosis Committee, Laboratory Medicine Branch, Chinese Medical Doctor Association
Standing Committee Member, Geriatrics Hematology Branch, Chinese Medical Association
Executive Director, World Federation of Chinese Medicine Societies
Member, Beijing Rare Disease Society
