Multiple myeloma is a blood cancer that arises from plasma cells, a type of white blood cell found in the bone marrow. These cancerous cells multiply uncontrollably, crowding out healthy blood cells and leading to complications such as bone damage, anemia, and kidney problems. Daratumumab is a targeted therapy that represents a significant advancement in treating multiple myeloma.
Daratumumab is a type of medication known as a monoclonal antibody, a laboratory-produced molecule engineered to serve as a substitute antibody. It is specifically designed to recognize and attach to a particular protein found on the surface of myeloma cells. This targeted approach allows it to initiate a precise attack against the cancer by enlisting the body’s own immune system. It is used for newly diagnosed patients as well as those whose cancer has returned after previous treatments.
Mechanism of Action Against Myeloma Cells
The effectiveness of daratumumab lies in its ability to target a protein called CD38. This protein is found in high amounts on the surface of multiple myeloma cells but at much lower levels on normal cells, making it an ideal target for therapy. Daratumumab is a human monoclonal antibody that seeks out and binds to this CD38 protein, marking the cancer cell for destruction.
Once daratumumab attaches to the CD38 protein, it triggers the immune system to attack the cancer cell through several distinct pathways. One primary method is called antibody-dependent cell-mediated cytotoxicity (ADCC). In this process, daratumumab acts like a flag, signaling immune cells, particularly Natural Killer (NK) cells, to the location of the myeloma cell. The NK cells then release cytotoxic substances that kill the flagged cancer cell.
Another mechanism is complement-dependent cytotoxicity (CDC). The complement system is a part of the immune system that enhances the ability of antibodies to clear microbes and damaged cells. When daratumumab binds to CD38, it activates this system, leading to the formation of a protein complex that punches holes in the myeloma cell’s membrane, causing it to rupture and die.
Beyond these direct killing mechanisms, daratumumab also has other effects. It can directly cause programmed cell death, or apoptosis, in the myeloma cells by binding to the CD38 protein. It also helps modulate the immune system by reducing the activity of other cells that might suppress the immune response, thereby enhancing the body’s overall ability to fight the cancer.
Treatment Administration and Regimens
Daratumumab is administered to patients in two primary forms: an intravenous (IV) infusion or a subcutaneous injection given under the skin. The IV infusion is delivered directly into a vein and can take several hours to complete. In contrast, the subcutaneous injection is a much faster process, taking only a few minutes to administer. The subcutaneous route often leads to fewer administration-related reactions and is more convenient for patients.
Daratumumab is uncommonly used as a standalone treatment. Instead, it is incorporated into a combination therapy regimen, where it works alongside other multiple myeloma drugs. Commonly used combinations include daratumumab with proteasome inhibitors like bortezomib, or with immunomodulatory agents such as lenalidomide, often accompanied by a corticosteroid like dexamethasone.
The treatment schedule for daratumumab is more intensive at the beginning of therapy and becomes less frequent over time. For example, a patient might receive the drug weekly for the first couple of months, then transition to every two weeks, and eventually to a maintenance schedule of once every four weeks. This tapering schedule is designed to maximize the initial impact on the cancer while minimizing long-term disruption to the patient’s life. Patients may continue on a maintenance regimen until the disease progresses or side effects become unmanageable.
The specific regimen chosen by the oncology team depends on several factors, including the patient’s overall health, prior treatments, and the genetic features of their myeloma. For newly diagnosed patients who are eligible for a stem cell transplant, daratumumab might be part of the initial therapy. For those not eligible for a transplant, it can be a core component of their initial treatment. In cases of relapsed or refractory myeloma, daratumumab-based combinations offer a valuable alternative.
Potential Side Effects
A notable side effect associated with daratumumab is the occurrence of infusion-related reactions, which are most common during the first administration. These reactions can include symptoms like chills, fever, shortness of breath, or a stuffy nose. To minimize this risk, healthcare providers administer pre-medications before the treatment begins, such as a corticosteroid, an antihistamine, and a fever reducer.
Beyond infusion reactions, patients may experience other side effects. Fatigue is a common complaint, as the body works to fight the cancer and cope with the treatment. Other reported issues include nausea, back pain, and an increased susceptibility to infections due to a decrease in white blood cells (neutropenia and lymphopenia).
A unique consideration for patients receiving daratumumab is its interference with blood testing procedures. The drug can bind to the CD38 protein on red blood cells, which can complicate blood typing and cross-matching tests required for a blood transfusion. Patients must inform their medical team and any blood banks that they are being treated with daratumumab. This allows the lab to use special techniques to ensure accurate test results.
While many side effects are manageable, the suppression of the immune system can lead to severe infections, such as pneumonia. Regular monitoring of blood counts is a standard part of care to watch for significant drops in white blood cells. Patients are also advised to be vigilant about signs of infection, such as fever or cough, and to report them to their doctor promptly.
Treatment Efficacy and Patient Monitoring
Clinical trials have demonstrated that adding daratumumab to standard treatment regimens for multiple myeloma leads to better outcomes. For both newly diagnosed individuals and those with relapsed disease, daratumumab has been shown to improve the depth of response to therapy. This means a higher percentage of patients see a significant reduction in cancer in their bodies, which translates into longer periods of progression-free survival.
One goal of treatment is to achieve a state known as minimal residual disease (MRD) negativity. This is a deep level of response where highly sensitive tests can no longer detect any myeloma cells in the bone marrow. Studies have found that patients treated with daratumumab-containing regimens are more likely to reach MRD-negative status, which is associated with a better long-term prognosis.
To track the effectiveness of the treatment, doctors rely on regular blood tests to measure the levels of abnormal proteins produced by the myeloma cells, known as M-protein and serum free light chains. A significant decrease in these markers indicates that the cancer is responding to the therapy. These tests are done before each treatment cycle to provide an ongoing assessment of the disease status.
In some cases, a bone marrow biopsy may be performed to get a more direct look at the cancer. This procedure involves taking a small sample of bone marrow to be examined in a laboratory. A biopsy can confirm the percentage of plasma cells in the marrow and can be used for MRD testing. The combination of blood tests and bone marrow assessments gives the healthcare team a comprehensive picture of how well the regimen is working.