Leo I. Gordon, M.D., is the Abby and John Friend Professor of Cancer Research and Professor of Medicine at Northwestern University in Chicago, IL.  He is Chief of the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine and Associate Director for Clinical Sciences at the Robert H. Lurie Comprehensive Cancer Center at Northwestern University.


Zevalin®(Ibritumomab tiuxetan) was the first radioimmunotherapy treatment to be approved by the U.S. Food and Drug Administration (FDA) for the treatment of non-Hodgkin's lymphoma.  Zevalin has been approved for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma, including patients with follicular non-Hodgkin's lymphoma who are no longer responding to treatment with Rituxan® (rituximab), a monoclonal antibody therapy.

Zevalin is different in many ways from conventional chemotherapy or external beam radiation therapy.  Zevalin combines the cell targeting ability of a monoclonal antibody with the additional cell killing ability of a radioactive particle, or radioisotope, called yttrium-90.  Treatment with the Zevalin regimen can be completed within a week on an outpatient basis.  It is generally well tolerated by patients, without the hair loss and nausea that often accompany chemotherapy treatments.  The most common side effect is a temporary reduction in blood cell counts.


Antibodies are normal components of the body's immune system that can recognize and destroy foreign invaders such as bacteria and viruses.

Scientists can now produce monoclonal antibodies designed to recognize very specific targets, or antigens, that are present on certain kinds of cancer cells.  Rituxan was the first monoclonal antibody to receive FDA approval.

Therapy with a monoclonal antibody is an effective way of specifically targeting certain kinds of cancer cells, with a low degree of toxicity to normal cells.  Monoclonal antibody therapy is administered by intravenous infusion, generally on an outpatient basis.  Once in the bloodstream, monoclonal antibodies travel throughout the body and attach themselves to cells that have the specific target antigen, such as cancer cells.  This alerts the body's own immune system to recognize and help destroy the cancer cells.  Although some normal cells that also have the specific target antigen may be affected along with the cancer cells, the body can replace these normal cells following treatment.

The monoclonal antibody used in the Zevalin regimen specifically recognizes and attaches to the CD20 antigen, which is found on the surface of lymphocytes, including the malignant B-lymphocytes in patients with B-cell non-Hodgkin's lymphoma.


Radioimmunotherapy is a new kind of cancer therapy, involving the combination of a monoclonal antibody with a radioisotope, as a source of radiation.  When a monoclonal antibody is combined with a radioisotope, it is said to be 'radiolabeled.'  With radioimmunotherapy, the radiolabeled antibody targets and binds to a specific antigen present on cancer cells, delivering a dose of radiation directly to the targeted cells.  Not only does the radiation destroy the cell to which it is bound, but it also destroys the surrounding cells, which is called the crossfire effect.


There are two products currently approved by the US Food & Drug Administration for radioimmunotherapy of patients with B-cell lymphomas: Zevalin and Bexxar®.  Both use radioactively-labeled mouse monoclonal antibodies binding to the CD20 antigen.


Bexxar employs Iodine-131, a radiation-emitting form of iodine, attached to the monoclonal antibody Tositumomab.  Tositumomab seeks out and binds to CD20, found on the surface of B-cells.  Once it is combined with lodine-131, Tositumomab is able to deliver its radiation to targeted cells. lodine-131 emits two forms of radiation.  Beta radiation is responsible for most of the tumor-killing effect and gamma radiation allows gamma camera scans to be performed to evaluate the distribution and clearance of radiation from the body. Iodine-131 radiation is eliminated from the body mainly through the urine and by the natural decay of lodine-131 (please see LRF’s Bexxar fact sheet for more information).

The Zevalin regimen uses two different radioisotopes, indium-111 and yttrium90. Indium-111 radiolabeled Zevalin is used for imaging studies.  By obtaining a series of images using a special camera called a 'gamma camera,' physicians can follow where Zevalin goes inside the body.  The amount of radiation associated with this imaging dose of indium-111 Zevalin is very small, and patients do not need to observe any special safety precautions following this part of the regimen.
For treatment, Zevalin is combined with the yttrium-90 radioisotope, a pure beta emitter.  The radiation from the therapeutic dose of yttrium-90 Zevalin is strong enough to damage and kill the targeted cancer cells and nearby cells, including some normal cells. 


The Zevalin regimen is delivered over the course of about a week on an outpatient basis.  Delivery of the regimen is coordinated by a team of healthcare professionals, including oncologists, nuclear medicine physicians or radiation oncologists, nurses, pharmacists, and technicians.  Because the Zevalin regimen involves the use of radioisotopes, it is necessary to involve persons specially trained in the safe handling of these substances at a licensed nuclear medicine or radiation oncology facility.

On day one, the patient first receives an intravenous infusion of Rituxan, which takes a few hours.  Following the Rituxan infusion, the patient will go to a nuclear medicine or radiation oncology facility to receive an imaging dose of indium-111 Zevalin.  This intravenous infusion will take approximately 10 minutes.  A nurse or technician will stay with the patient during treatment.

On day one or day two, whole body images will be taken with a gamma camera.  Then, on day two or day three, additional images will be taken with the gamma camera.  The physician may recommend that additional images be taken on day four or five, between 90 to 120 hours after the infusion of indium-111 Zevalin.  The physician uses these images to view the path of indium-111 Zevalin in the body.

Approximately one week after the initial treatment day, the patient will return for a second infusion of Rituxan followed by yttrium-90 Zevalin, the therapeutic portion of the Zevalin regimen.  After receiving-Rituxan, the patient will again go to the nuclear medicine or radiation oncology facility, this time to receive yttrium-90 Zevalin.  Yttrium-90 Zevalin is administered by an intravenous infusion that is completed in about 10 minutes.  Imaging studies are not necessary after this infusion.


Radiation from yttrium-90 Zevalin does not penetrate outside the body, but a small amount of radiation may be present (for about a week following treatment) in body fluids, such as blood and urine.  Minimal radiation safety precautions are required.  Patients should wash their hands thoroughly after urination and use a condom during sexual intercourse.  In general, it is not necessary to avoid contact with friends or family during this time, and isolation is not required.  Patients can usually return to work and their usual activities following treatment.  Patients should speak with their physician regarding recommended safety precautions and any questions or concerns that they may have. 


Because the Zevalin regimen involves the administration of Rituxan, side effects of Rituxan and Zevalin are discussed.  The most common side effects associated with Rituxan are mild, flu-like symptoms.  Physicians will often provide medications such as Tylenol and Benadryl to manage these temporary side effects. 

The administration of yttrium-90 Zevalin usually results in no infusion-related toxicities.  However, because of the radioactivity of this treatment, blood cell counts will be lowered.  The period of lowered blood cell counts generally occurs 4 to 6 weeks following therapy, with recovery of counts 2 to 3 weeks later.  It is important to note that Zevalin is not associated with hair loss or with the nausea and vomiting typically seen with chemotherapy cycles.


Zevalin has been approved for the treatment of patients with relapsed or refractory B-cell lymphomas of the following subtypes: low-grade and/or follicular, or transformed B-cell non-Hodgkin's lymphoma, including patients who are no longer responding to Rituxan treatment.  Zevalin is not currently recommended for patients with greater than 25% bone marrow involvement, impaired bone marrow reserve or for patients with platelet counts less than 100,000. 


In clinical trials involving patients with low-grade non-Hodgkin's lymphoma, the reported response rates to Zevalin have been 70% to 80%.  Zevalin produced responses in patients who were no longer responding to treatment with chemotherapy, were no longer responding to treatment with Rituxan, and those who had bulky disease. 

In a randomized Phase III clinical trial for patients with relapsed and refractory indolent lymphoma, comparing Rituxan and Zevalin treatments, 50% of patients responded to Rituxan and 80% of patients responded to Zevalin.  The patients who were treated with Zevalin had a complete response rate of 30%, compared to 20% of Rituxan patients. Patients had a median age of 60, with an average of two prior therapies.  The median duration of response was 13.9 (1.0-30.1) months with Zevalin compared to 11.8 months (1.2-24.5) with Rituxan.  The subgroup of patients with follicular lymphoma had a median duration of response of 16.7 months.  Importantly, there are patients who are still in remission over 5 years after treatment with a single dose of Zevalin.


It is not believed that Zevalin will limit future treatment options.  Data reported that NHL treatments such as chemotherapy, Rituxan, radiation therapy and stem cell transplant are all feasible following Zevalin therapy (Ansell et al, JCO Sept. 2003).


To learn more about lymphoma, treatments and ongoing clinical trials, contact LRF’s Lymphoma Helpline at 1-800-500-9976, or visit

For more information about Zevalin, please consult Zevalin Prescribing Information, call 1- 877-433-4332, visit or speak with your physician. 
Last updated December 2004