Epcoritamab is a targeted therapy for certain blood cancers. It works by harnessing the body’s own immune system to fight malignant cells, offering a new treatment option.
Understanding Diffuse Large B-cell Lymphoma (DLBCL)
Diffuse Large B-cell Lymphoma (DLBCL) is a common, aggressive type of non-Hodgkin lymphoma. This cancer originates in B-lymphocytes, a type of white blood cell. DLBCL can develop in the lymph nodes, located throughout the body, or in areas outside the lymph nodes such as the gastrointestinal tract, skin, or bone.
It is the most prevalent non-Hodgkin lymphoma globally, accounting for approximately 25-30% of all cases. While it can affect individuals of any age, it is more frequently diagnosed in older adults, with a median age around 70 years. DLBCL often leads to symptoms like enlarging masses, sometimes accompanied by fever, night sweats, or unexplained weight loss.
How Epcoritamab Works
Epcoritamab functions as a bispecific antibody, engineered to bind to two different targets simultaneously. One part attaches to CD3, a protein on T-cells. The other part binds to CD20, a protein on malignant B-cells, including those in lymphoma.
This dual binding brings T-cells into close contact with cancerous B-cells. This proximity activates T-cells, prompting them to release cytotoxic granules and signaling molecules called cytokines. These substances then induce programmed cell death in the targeted lymphoma cells. This mechanism, known as T-cell redirection, helps the immune system eliminate cancer cells.
Administering Epcoritamab
Epcoritamab is administered via subcutaneous injection. The treatment schedule involves a step-up dosing approach during the first cycle to manage potential side effects. For instance, in Cycle 1, patients may receive a small dose of 0.16 mg on Day 1, followed by 0.8 mg on Day 8, and then the full dose of 48 mg on Day 15 and Day 22.
After the initial cycle, dosing frequency changes: 48 mg weekly during Cycles 2 and 3, every other week during Cycles 4 through 9, and every four weeks from Cycle 10 onwards. Treatment continues until disease progression or unacceptable side effects.
Epcoritamab received accelerated approval from the U.S. Food and Drug Administration (FDA) in May 2023 for adults with relapsed or refractory Diffuse Large B-cell Lymphoma (DLBCL) not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma. This approval is for patients who have received two or more prior lines of systemic therapy. Initial doses, especially the first full 48 mg dose, should be administered in a specialized healthcare setting where patients can be monitored for at least 24 hours due to the potential for severe reactions.
Expected Outcomes and Managing Side Effects
Clinical trials show Epcoritamab’s effectiveness in relapsed or refractory DLBCL. In the EPCORE NHL-1 study, the overall response rate was 61%, with 38% of patients achieving a complete response. Longer-term follow-up indicated an overall response rate of 59% and a complete response rate of 41%, with a median duration of complete response of 36.1 months.
A common and serious side effect is Cytokine Release Syndrome (CRS), occurring in 51% of patients in trials, with most cases being low-grade (Grade 1 or 2). CRS is a systemic inflammatory response causing symptoms like fever, low blood pressure, difficulty breathing, chills, headache, and a rapid heart rate. Management involves supportive care, sometimes with medications like tocilizumab.
Another serious side effect is Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), occurring in 6% of patients in trials. ICANS can manifest as changes in consciousness, confusion, tremors, dizziness, or coordination problems. Both CRS and ICANS typically occur early in treatment, often after the first full dose, requiring close monitoring. Other common side effects include fatigue, musculoskeletal pain, injection site reactions, fever, abdominal pain, nausea, and diarrhea. Infections, including serious ones, have been observed, and prophylactic antimicrobials may be administered.