Isatuximab is a targeted therapy and monoclonal antibody used to treat multiple myeloma, a type of blood cancer. This laboratory-produced protein attaches to specific targets on cancer cells to help fight the disease.
Understanding Multiple Myeloma
Multiple myeloma is a cancer originating in plasma cells, a type of white blood cell found in the bone marrow. Healthy plasma cells produce antibodies to fight infections.
In multiple myeloma, cancerous plasma cells multiply abnormally, crowding out healthy blood cells. These abnormal cells produce dysfunctional proteins that can damage organs, especially the kidneys. The disease also weakens bones, causing pain and fractures. Patients may also experience fatigue, increased infections, and low blood cell counts like anemia.
How Isatuximab Targets Cancer Cells
Isatuximab targets CD38, a protein highly expressed on multiple myeloma cells. This monoclonal antibody attaches to CD38, initiating actions that destroy cancer cells.
Isatuximab triggers the immune system to attack myeloma cells through antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP), recruiting immune cells like natural killer (NK) cells and macrophages. It also induces complement-dependent cytotoxicity (CDC), where immune system proteins directly puncture and kill myeloma cells.
Additionally, Isatuximab directly causes myeloma cell death via apoptosis (programmed cell death). It also inhibits CD38’s ectoenzymatic activity, which can have immunosuppressive effects in the bone marrow.
Receiving Isatuximab Treatment
Isatuximab is administered intravenously (into a vein) in cycles. Infusion frequency varies by cycle and medication combination. Patients receive premedications like corticosteroids and antihistamines before each infusion to reduce infusion-related reactions.
For the first 28-day cycle, Isatuximab is given weekly on Days 1, 8, 15, and 22. In subsequent cycles, frequency may decrease to once every two weeks, typically on Days 1 and 15 of a 28-day cycle. The first infusion can take about 3 hours and 20 minutes, while later infusions may be shorter, around 75 minutes, if no reactions occur.
Isatuximab is often combined with other medications to enhance effectiveness. Common combinations include pomalidomide and dexamethasone; carfilzomib and dexamethasone; and bortezomib, lenalidomide, and dexamethasone for newly diagnosed patients not eligible for stem cell transplant. Treatment continues until disease progression or unacceptable side effects.
Common Side Effects and Management
Patients receiving Isatuximab may experience side effects, with infusion-related reactions being common. Symptoms include fever, chills, shortness of breath, nausea, and blood pressure changes, occurring during or shortly after infusion. Premedications are given, and infusion rates may be adjusted or paused to manage these.
Blood count changes are also common. These include neutropenia (decreased white blood cells, increasing infection risk), anemia (reduced red blood cells, causing fatigue), and thrombocytopenia (decreased platelets, leading to bruising/bleeding). Regular blood tests monitor counts, and supportive care like growth factors or transfusions may be provided.
Other common side effects are infections (especially upper respiratory and pneumonia) due to immune system effects, fatigue, and gastrointestinal issues like diarrhea, nausea, and vomiting. These are managed with supportive measures such as hydration, dietary adjustments, and anti-nausea medications. Patients should report any side effects to their healthcare team.