Carfilzomib, known by its brand name Kyprolis, is a targeted therapy medication used to treat multiple myeloma. This type of cancer originates in plasma cells, which are a type of white blood cell found in the bone marrow. In multiple myeloma, these abnormal plasma cells multiply uncontrollably, producing unusual proteins and crowding out healthy cells in the bone marrow. Carfilzomib helps manage this condition by specifically targeting these cancerous cells.
How Carfilzomib Works
Carfilzomib functions as a proteasome inhibitor, a drug that interferes with cellular processes. Imagine the proteasome as the cell’s “garbage disposal” or “recycling center,” responsible for breaking down unneeded or damaged proteins. This process is important for maintaining cellular balance and regulating cell growth.
Multiple myeloma cells are highly active in producing large quantities of abnormal proteins, making them particularly reliant on the proteasome for their survival. Carfilzomib works by irreversibly blocking or “clogging” this cellular garbage disposal system. It targets the chymotrypsin-like activity of the 20S proteasome, the core part responsible for protein breakdown.
This targeted inhibition leads to an accumulation of misfolded and damaged proteins within the cancer cells. The buildup of these toxic proteins stresses the cells, triggering apoptosis (programmed cell death). Normal cells are less affected because they are not as dependent on the proteasome for protein disposal, allowing carfilzomib to selectively target the myeloma cells.
The Treatment Process
Carfilzomib is administered as an intravenous (IV) infusion, delivered directly into a vein, typically in a hospital or clinic setting. The duration of each infusion can vary, but it commonly takes about 10 to 30 minutes. Patients receive the medication according to a specific schedule, which is often structured into 28-day cycles.
A common treatment schedule involves administering carfilzomib on specific days within this cycle, such as two consecutive days a week for three weeks, followed by a one-week rest period. For example, a patient might receive the infusion on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle, with variations in dosage over time. Exact treatment schedules and dosages, which can range from 20 mg/m² to 70 mg/m², are tailored to individual patient needs and may differ.
Patients usually receive pre-medications, such as dexamethasone, a steroid, at least 30 minutes but no more than 4 hours before each carfilzomib dose in the first cycle. This helps to reduce the likelihood of infusion reactions. Adequate hydration with both oral and intravenous fluids is also recommended before and after each treatment, especially in the first cycle, to support kidney function and reduce the risk of complications. Throughout the treatment course, regular blood tests are conducted to monitor blood counts, kidney function, and liver function, allowing the medical team to adjust the plan as needed.
Potential Side Effects
Common Side Effects
Patients receiving carfilzomib may experience various side effects, with some being more frequent but generally manageable. Fatigue is a common occurrence, alongside gastrointestinal issues such as nausea and diarrhea. Some individuals may also report shortness of breath or experience fever.
Blood count changes are also observed, including low red blood cell counts (anemia) and low platelet counts (thrombocytopenia), which can lead to increased bruising or bleeding. These common effects are typically monitored by the healthcare team, and strategies are often employed to help manage them. Infusion-related reactions, characterized by symptoms like fever, chills, or muscle pain, can occur during or within 24 hours of administration.
Serious Side Effects
While less common, some side effects can be more serious and require immediate medical attention. Heart problems, including new-onset or worsening heart failure, have been reported, with symptoms such as chest pain, swelling in the extremities, or difficulty breathing. High blood pressure (hypertension) can also develop or worsen, potentially causing headaches or blurred vision.
Kidney problems, including sudden kidney failure, are a concern, often indicated by a decrease in urine output, swelling, or unusual tiredness. Lung issues, such as pulmonary hypertension or acute respiratory distress syndrome, may manifest as increased shortness of breath, wheezing, or fatigue. Tumor lysis syndrome, a condition where dying cancer cells release their contents into the blood, can also occur, presenting with symptoms like rapid weight gain, muscle cramps, or changes in urination.
Patients should promptly report any new or worsening symptoms to their medical team. The healthcare providers will closely monitor for these potential effects throughout the treatment period.
Efficacy and Use in Treatment Plans
Carfilzomib is primarily used in patients whose multiple myeloma has returned after previous treatments or has not responded to other therapies, a condition known as relapsed or refractory multiple myeloma. Its effectiveness has been demonstrated in various clinical studies for this patient population. It is rarely administered as a standalone treatment; instead, it is typically incorporated into combination regimens to enhance its effectiveness.
A common and effective combination involves carfilzomib with lenalidomide and dexamethasone, often referred to as “KRd”. Clinical trials have shown that regimens including carfilzomib can lead to deeper and more lasting responses, improving outcomes such as progression-free survival for many patients. For example, studies have reported overall response rates ranging from 78.4% to 90% in patients receiving carfilzomib-based combinations.
Median progression-free survival, which is the time patients live without their disease worsening, has been observed to be around 19.8 to 26.3 months in patients treated with KRd. While carfilzomib offers significant benefits, individual results can vary based on factors such as a patient’s overall health, the specific characteristics of their disease, and prior treatments. Patients should engage in discussions with their oncology team to understand the expected outcomes for their specific situation.