Elranatamab, marketed as Elrexfio, is a targeted immunotherapy medication designed to work with the body’s immune system to combat cancer. This drug offers a new approach for patients with specific, hard-to-treat cancers. Unlike traditional chemotherapy, elranatamab precisely targets cancer cells, allowing for a more focused attack that harnesses the patient’s immune system to fight the disease.
What Elranatamab Treats
Elranatamab is approved for the treatment of multiple myeloma, a cancer that forms in a type of white blood cell called a plasma cell. Healthy plasma cells are found in the bone marrow and are a component of the immune system. In multiple myeloma, cancerous plasma cells accumulate in the bone marrow, crowding out healthy blood cells and producing abnormal proteins. This can lead to bone pain, fractures, fatigue, and frequent infections.
The medication is for patients with “relapsed or refractory” multiple myeloma. Relapsed means the cancer has returned after treatment, while refractory means it did not respond to the initial treatment. Elranatamab is considered for individuals who have undergone several other treatments. The U.S. Food and Drug Administration (FDA) has approved it for adults who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
The clinical trial that led to its approval, MagnetisMM-3, focused on patients with this extensive treatment history. The results showed that a portion of these heavily pretreated patients responded to the therapy, demonstrating its potential in this clinical setting.
How Elranatamab Works
Elranatamab is a bispecific antibody, a molecule engineered to bind to two different targets simultaneously. This dual-targeting capability allows it to act as a molecular bridge, connecting a patient’s immune cells directly to cancer cells. This mechanism is a type of immunotherapy known as a bispecific T-cell engager (BiTE).
One arm of the elranatamab antibody attaches to a protein called B-cell maturation antigen (BCMA). BCMA is found in high quantities on the surface of multiple myeloma cells but is less common on healthy cells, making it an effective target. By targeting BCMA, the drug selectively seeks out the cancerous plasma cells. This specificity helps to focus the immune attack directly on the source of the cancer.
The other arm of the antibody binds to CD3, a protein on the surface of T-cells. T-cells are a type of immune cell that can kill other cells, including cancerous ones. By bringing a T-cell into direct contact with a myeloma cell, elranatamab activates the T-cell. This activation triggers the T-cell to release cytotoxic molecules that destroy the tethered myeloma cell.
This process turns the patient’s own immune system into a guided weapon against multiple myeloma. The drug doesn’t kill cancer cells directly but facilitates the process by ensuring the T-cells find and eliminate their targets. This approach differs from CAR T-cell therapy because it uses the patient’s existing T-cells without needing to collect and engineer them outside the body, which can shorten the time to treatment.
Administration and Dosing
Elranatamab is administered as a subcutaneous injection into the fatty tissue just under the skin, in the abdomen or thigh. The dosing schedule is structured to manage the body’s response to the medication.
A feature of its administration is the “step-up dosing” schedule. Patients do not receive the full therapeutic dose from the start. Instead, they begin with a small initial dose, followed by a larger second dose, before reaching the full treatment dose. For example, the first dose might be 12mg, the second 32mg, and the full weekly treatment dose 76mg.
This gradual increase is designed to reduce the risk and severity of initial side effects, particularly cytokine release syndrome. Because of the potential for reactions during this initial phase, patients are hospitalized for monitoring. This may involve a 48-hour stay after the first dose and a 24-hour stay after the second. After completing the step-up phase and 24 weeks of weekly treatment, responding patients may transition to a less frequent maintenance schedule, receiving the injection once every two weeks.
Potential Side Effects and Management
Treatment with elranatamab carries the risk of side effects, highlighted by a black box warning from the FDA. The most serious of these are Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). These conditions require close medical supervision when starting treatment.
CRS is a systemic inflammatory response that can occur when T-cells are activated and release a large flood of inflammatory molecules called cytokines. This can cause a range of symptoms, including fever, headache, a drop in blood pressure, and difficulty breathing. Management of CRS depends on its severity and may involve supportive care or medications to counteract the inflammatory response.
ICANS is a neurological condition that affects the brain and nervous system. Patients may experience symptoms such as confusion, difficulty speaking, loss of coordination, or seizures. The onset of these neurological toxicities requires immediate medical attention.
Beyond these risks, patients may experience other common side effects. The drug can also suppress the bone marrow’s ability to produce healthy blood cells, which can increase the risk of infection and bleeding. Other side effects include:
- Fatigue
- Diarrhea
- Muscle and bone pain
- Reactions at the injection site, such as redness or swelling
- Anemia (low red blood cells)
- Neutropenia (low white blood cells)
- Thrombocytopenia (low platelets)