Multiple Myeloma

Multiple myeloma is a cancer of plasma cells, a type of white blood cell found in bone marrow and normally responsible for producing antibodies. When advanced, bone pain and bone fractures, anemia (low red blood cell count), hypercalcemia (high level of calcium in the blood) and kidney failure may occur.

Multiple myeloma is treated using chemotherapeutic agents and, in some cases, stem cell transplantation. In addition, biphosphonates and radiation therapy are sometimes used to reduce pain from bone lesions.

Despite ever better treatments, multiple myeloma remains incurable and, while improved, the 5-year relative survival rate is on average 50%. During this period, patients may relapse several times and require new rounds of treatment.

Myeloma Cast Nephropathy

Severe acute kidney injury affects 20% to 25% of myeloma patients at diagnosis and up to 50% of patients over the course of the disease. In the vast majority of cases, it is caused by the precipitation of protein aggregates, called myeloma casts, in the renal tubules.
The formation of myeloma casts results from interactions between light chains, which are synthesized by the myeloma cells and filtered by the kidney, and uromodulin, which is a protein normally present in the urine. These casts typically form in patients with heavy tumor burden and high amounts of light chains in the urine, and their formation is often triggered by a precipitating event such as an infection, an episode of dehydration, or exposure to contrast agents or drugs such as NSAIDs. Myeloma casts obstruct the nephron, leading to acute kidney injury and induce an inflammatory reaction that leads to fibrosis and irreversible chronic kidney damage.

The consequences of myeloma cast nephropathy to the patient and the health care system can be severe. It is associated with increased mortality during induction therapy. It is also associated with lower response to treatment and lower overall survival, probably because it restricts the aggressiveness with which the oncology team can treat the underlying myeloma. From a hospital perspective, myeloma cast nephropathy can be responsible for longer hospital stays, higher dialysis rates and increased overall costs.

Thrasos THR-8590 will be targeted initially at the 30% of multiple myeloma patients who have cast nephropathy and a severe reduction in kidney function.