Due to its low incidence and diverse clinical manifestations, patients with AL amyloidosis are often misdiagnosed or underdiagnosed, resulting in insufficient treatment. From January 26th to 28th, 2024, the “China Society of Clinical Oncology (CSCO) Leukemia Expert Committee, Lymphoma Expert Committee, and Myeloma Preparatory Committee Working Meeting, and the 2024 CSCO Hematology, Lymphoma, and Myeloma Disease Academic Conference” was successfully held in Haikou. During the conference, Professor Shuye Wang from the First Affiliated Hospital of Harbin Medical University shared insights with Oncology Frontier – Hematology Frontier on the current status of diagnosis and treatment of systemic amyloidosis, perspectives on early diagnosis, and the future research plans of his team.
Oncology Frontier – Hematology Frontier: Could you please elaborate on the current status of treatment, diagnosis, and treatment strategies for systemic amyloidosis?
Professor Shuye Wang: Systemic immunoglobulin light chain (AL) amyloidosis, also known as primary amyloidosis, is a clinical syndrome characterized by the deposition of large amounts of immunoglobulin light chains in the form of amyloid fibers in various organs of the body, leading to gradual organ failure. The most affected organs are the kidneys, followed by the heart, liver, skin, and tongue, among others, which can lead to organ failure and even life-threatening conditions. Due to its rarity, systemic amyloidosis has received relatively little attention in the past. However, with the advancement of science and technology and the improvement of diagnostic and treatment levels, although systemic amyloidosis is rare, it is not uncommon in clinical practice. Early diagnosis and treatment of AL amyloidosis are crucial for medical practitioners because early diagnosis and timely treatment can lead to cure and prolonged survival for some patients.
Regarding the treatment of systemic amyloidosis, there are already some new methods available. Once systemic amyloidosis is diagnosed, the challenge lies in how to treat it. For example, in the case of renal amyloidosis leading to renal failure or even uremia, symptomatic treatment is the only option, including dialysis or medications for renal diseases. However, with the advent of targeted drugs or new therapies, the diagnostic and treatment levels of systemic amyloidosis have greatly improved. For instance, in cardiac amyloidosis, where there is thickening of the interventricular septum and patients develop heart failure, leading to respiratory distress and ultimately cardiopulmonary failure, recent advancements such as the introduction of daratumumab (DARA), an anti-CD38 monoclonal antibody, have shown promising results. While DARA has demonstrated significant efficacy in the treatment of multiple myeloma, its efficacy in amyloidosis has been less satisfactory. The recent launch of daratumumab subcutaneous formulation (DARA SC) has reduced the patient’s infusion burden and subsequently reduced cardiac damage, with rapid onset of efficacy (within approximately one week). This has led to a change in frontline treatment decisions, increasing the cure rate of amyloidosis to 50-60%. However, there are still many issues to be addressed, such as organ damage caused by amyloidosis, which requires symptomatic treatment. After the application of new drugs, the clearance or reduction of amyloidosis-related substances may bring significant benefits to organ damage. We also believe that more new drugs will achieve success in amyloidosis in the future.
Oncology Frontier – Hematology Frontier: What insights can you share regarding the early diagnosis of amyloidosis?
Professor Shuye Wang: As mentioned earlier, amyloidosis is a rare disease that has received relatively little attention in the past. However, with the development of science and technology and the improvement of diagnostic and treatment levels, systemic amyloidosis, although rare, is not uncommon in clinical practice. Early diagnosis of amyloidosis is challenging. Compared to lymphoma, which is relatively easy to diagnose based on observable organ damage such as lymphadenopathy or skin nodules, amyloidosis is more insidious. For example, early manifestations of renal involvement may present as proteinuria and renal insufficiency, often diagnosed as renal disease rather than amyloidosis, requiring a pathological biopsy for diagnosis. Similarly, early manifestations of cardiac amyloidosis may be diagnosed as hypertrophic cardiomyopathy or coronary artery disease. Further examinations such as echocardiography, magnetic resonance imaging, and ECT may confirm the diagnosis of amyloidosis, such as myocardial hypertrophy or interventricular septal thickness >12 mm, which may require a pathological biopsy for confirmation. Biopsy of other sites, such as amyloid deposition in the tongue or skin lesions, can also be diagnosed through pathological examination. By combining pathological diagnosis, clinical indicators, and laboratory tests, a diagnosis of amyloidosis can be established.
Oncology Frontier – Hematology Frontier: What prompted you to focus on rare diseases such as amyloidosis?
Professor Shuye Wang: Amyloidosis is a multidisciplinary disease. In the past, amyloidosis was often discovered in advanced stages, with the most common manifestation being renal failure. When renal disease suspected to be related to hematologic diseases, multiple myeloma or metastases are most likely considered. However, the diagnosis of amyloidosis requires biopsy confirmation from relevant sites, such as early presentation of proteinuria (++ to +++), which may be diagnosed as nephrotic syndrome or nephritis, and further examination may reveal the possibility of amyloidosis. Additionally, amyloidosis may also be discovered in the cardiology department, where patients present with cardiac hypertrophy and heart failure. After a series of examinations, the cardiology department may determine that it is not hypertrophic cardiomyopathy or coronary artery disease. Furthermore, when there is an increase in blood immunoglobulin levels, a “big biochemical” examination (comprehensive examination of blood components through biological or chemical methods to detect latent diseases, screen for specific diseases, and assist in disease diagnosis. Big biochemical examination mainly includes liver function, renal function, electrolytes, blood sugar, blood lipids, cardiac enzymes, etc.) with immunoglobulin levels exceeding 40g/L should raise suspicion of hematologic diseases, as many cases of multiple myeloma are detected early through biochemical examinations during physical examinations. Early examination, early diagnosis, and early treatment can greatly improve patient survival rates, as is the case with amyloidosis. When hematologists observe high immunoglobulin levels and positive urine protein, further investigation is essential, particularly focusing on the early detection of monoclonal immunoglobulin proliferation.
Oncology Frontier – Hematology Frontier: What research plans do you and your team have for the future?
Professor Shuye Wang: While doctors often focus on clinical research, it is equally important to conduct scientific research and drug development. For example, how to reduce organ amyloidosis, how to combine treatment with other drugs, and how to use more precise targeted drugs to increase cure rates to over 80% or even 90%. Our hospital (the First Affiliated Hospital of Harbin Medical University) has established a multidisciplinary team (MDT) for plasma cell diseases, jointly treating patients with pathology, cardiovascular internal medicine, nephrology, orthopedics, ultrasound imaging, and other disciplines, conducting clinical analysis and research, and then transferring the findings to basic research conducted by doctors in research positions. For instance, after observing early cardiac damage, we can biopsy a small amount of cardiac tissue and perform molecular testing and single-cell sequencing, including testing of renal tissue, to discover new issues. Our team, with the support of the hospital director, has held four hospital-wide MDT meetings in this area over the past two years. MDT meetings have greatly improved the diagnostic and treatment levels of doctors, benefiting patients more. Currently, our hematology department has two MDT teams: a plasma cell disease MDT team and a central nervous system large B-cell lymphoma MDT team. Therefore, it is essential to pay attention to the construction of MDT teams, which is crucial for medical workers in clinical work, experimental research, and benefiting patients.
We thank Oncology Frontier – Hematology Frontier for bringing better goals and directions to our hematology field, providing us with more opportunities for publicity, allowing hematologists to benefit more, and enabling patients to receive better diagnosis and treatment. Serving humanity is the common aspiration of every medical worker and media worker, enabling more patients to survive long-term or even be cured, and making greater contributions to the country. This is the heartfelt voice of all medical workers.
Professor Shuye Wang
Director of Hematology Department, First Affiliated Hospital of Harbin Medical University
Director of Lymphoma Ward, Professor, Chief Physician
