Ibritumomab Tiuxetan, known by its brand name Zevalin, is a radioimmunotherapy drug. This targeted therapy combines cell targeting with radiation delivery.
Understanding Ibritumomab Tiuxetan
Ibritumomab Tiuxetan combines a monoclonal antibody with a radioactive isotope. The monoclonal antibody, ibritumomab, identifies and attaches to the CD20 protein on the surface of both normal and malignant B-cells.
Once the antibody binds to the CD20 antigen, the attached radioactive isotope, yttrium-90 (Y-90), delivers localized radiation directly to these targeted B-cells. Y-90 is a beta-particle emitter, releasing high-energy electrons that damage cell DNA, leading to cell death. This direct delivery of radiation minimizes exposure and harm to surrounding healthy tissues.
For diagnostic purposes, Indium-111 (In-111) can be used with ibritumomab tiuxetan. In-111 allows for imaging of the drug’s distribution within the body before the therapeutic Y-90 dose, confirming the antibody reaches target cells.
Medical Conditions Treated
Ibritumomab Tiuxetan is approved for specific forms of non-Hodgkin lymphoma (NHL), a type of cancer that originates in lymphocytes, a kind of white blood cell. It is primarily used for adult patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin lymphoma. This includes individuals whose lymphoma has returned after previous treatment or has not responded to other therapies.
The medication is also approved for patients with previously untreated follicular NHL who have achieved a partial or complete response to initial chemotherapy. As consolidation therapy, it aims to eliminate remaining malignant cells and extend remission.
The Treatment Process
Ibritumomab Tiuxetan administration is a multi-step process, typically spanning several days. The regimen begins with an intravenous infusion of unconjugated rituximab, an antibody targeting CD20-positive B-cells. This clears circulating normal B-cells, enhancing subsequent distribution of radiolabeled ibritumomab tiuxetan to tumor cells.
A few days later, usually on Day 7, 8, or 9, a second dose of rituximab is administered. Following this second rituximab infusion, typically within four hours, the therapeutic dose of Yttrium-90 Ibritumomab Tiuxetan is given as a slow intravenous injection, often over 10 minutes. The exact dosage of Y-90 Ibritumomab Tiuxetan is determined by the patient’s body weight and platelet count, with a maximum allowable dose of 32 mCi regardless of weight.
Prior to each rituximab infusion, patients typically receive pre-medications like acetaminophen and diphenhydramine to help prevent infusion-related reactions such as fever, chills, or nausea. Blood counts are closely monitored throughout the treatment process to assess the patient’s response and manage potential side effects.
Potential Side Effects and Management
Treatment with Ibritumomab Tiuxetan can lead to various side effects, with hematologic toxicities being among the most common. Patients may experience low blood cell counts, including neutropenia (low white blood cells, increasing infection risk), thrombocytopenia (low platelets, increasing bleeding risk), and anemia (low red blood cells, causing fatigue and weakness). These effects are monitored through regular blood tests, and management may include supportive care like growth factors or transfusions if counts become severely low.
Other common side effects include fatigue, nausea, abdominal pain, and fever. Patients might also experience infusion-related reactions during rituximab administration, such as difficulty breathing, itching, facial swelling, or chills. These reactions are often mitigated by pre-medications.
Less frequent but more serious side effects can occur. These include the rare development of secondary malignancies, such as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), which are bone marrow disorders. Severe skin reactions, such as Stevens-Johnson syndrome, have also been reported, appearing days to months after infusion. Patients are advised to report any new or worsening symptoms to their healthcare team promptly for appropriate management and intervention.