Clinical trial shows promise for treating one form of the rare disorder
Amyloidosis is a rare disorder that occurs when certain cells in the body produce an abnormal protein, called amyloid, that accumulates in the body’s organs. Different cell types can cause different types of amyloidosis.
The protein becomes problematic because it is “misfolded,” or badly misshapen, and can build up and cause malfunction in different organs, including the lung, skin, bladder, bowel, heart, kidneys or nervous system. Excess amyloid protein, especially in the heart, kidney, or nervous system, is potentially life-threatening and can reduce your heart’s ability to pump enough blood, lead to kidney failure and dialysis, or damage the nerves that control blood pressure.
While amyloidosis is not cancer, it is sometimes treated with standards of “cancer-combat” care, and people with multiple myeloma – a blood cancer that begins in the bone marrow – may be at a higher risk for developing amyloidosis.
“Patients with multiple myeloma or its precursor disorders are at higher risk for amyloidosis because the abnormal plasma cells produced by multiple myeloma can, in certain circumstances, accumulate and deposit as so-called AL-amyloid,” explains Jens Hillengass, MD, PhD, Chief of Myeloma, Professor of Oncology and Medicine at Roswell Park Comprehensive Cancer Center.
“In ATTR amyloidosis, liver cells produce the misfolded protein, and in AA amyloidosis the protein is produced during chronic inflammation. ATTR amyloidosis can be hereditary or occur de novo, while AA amyloidosis is associated with chronic autoimmune diseases.”
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How is amyloidosis treated?
Treatment depends on the type of amyloidosis, how the rogue amyloid protein presents in the body and may include immunotherapy and/or chemotherapy, surgery and radiation therapy – or a combination of the three.
AL amyloidosis is a disorder of plasma cells, the white blood cells that produce immunoglobulins (antibodies that fight infection). This type of the illness produces too many plasma cells, like multiple myeloma, so a baseline treatment is a combination immune-chemotherapy. Medications are given with an injection, orally, and intravenously to destroy abnormal cells, just like they would be given to patients with multiple myeloma cancer.
Some people with AL amyloidosis benefit from a high-dose chemotherapy and blood stem cell transplant. This treatment destroys the plasma cells that produce amyloid protein with high doses of chemotherapy, then replaces them with highly specialized hematopoietic stem cells that develop into healthy bone marrow.
New treatment for AL amyloidosis now at Roswell Park
While chemotherapy and stem cell transplant focus on eliminating the plasma cells or bone marrow that produce the abnormal protein, a new treatment now available through a clinical trial at Roswell Park takes a different approach, aiming to clear the amyloid protein from the body which is usually a very slow process.
The phase 3 AFFIRM-AL Study, to measure the safety and efficacy of an investigational monoclonal antibody drug called birtamimab in the treatment of AL amyloidosis, is underway and accepting participants.
The multi-site trial is designed to determine how well birtamimab targets and clears the amyloid protein that causes cardiac dysfunction and failure in newly diagnosed patients with Mayo stage IV light chain (AL) amyloidosis.
To be eligible for enrollment, patients must be 18 years of age and meet the following additional criteria:
- Newly diagnosed with AL amyloidosis that affects the heart, but have not begun treatment
- Planned first-line chemotherapy containing bortezomib
- Adequate bone marrow reserve and liver and kidney function
“Birtamimab has been specifically developed for this purpose and has not been used in any other disease before,” Dr. Hillengass says. “Since this drug is in an early phase of development, it is difficult to predict if it will add benefit to the standard of care, but if it can help clearing the amyloid from the heart, this might have a tremendous benefit for patients diagnosed with AL amyloidosis.”