What is ZEVALIN?
ZEVALIN is a treatment for FL that combines two effective therapies in a single course of treatment: Immunotherapy and Radiotherapy.
Immunotherapy uses the immune system to fight diseases such as cancer.1
Immunotherapy uses antibodiesAntibodies
Proteins made by white blood cells in response to an antigen (a substance that causes the body to make a specific immune response). Each antibody can bind to only one specific antigen. The purpose of this binding is to help destroy the antigen. that can identify and attach to specific antigens. An antigenAntigen
Any substance that causes the body to make a specific immune response. is any substance that causes the body to make a specific immune response.2 For example, a CD20 antigen is expressed on pre-B and mature B lymphocytes and on >90% of B-cell non-Hodgkin's lymphomas.3 Once attached, antibodies recruit other parts of the immune system to destroy the cells containing the antigen.4
The ZEVALIN regimen includes two immunotherapy agents, rituximabRituximab
A drug used to treat certain types of B-cell non-Hodgkin's lymphoma. Rituximab binds to a protein called CD20, which is found on B-cells, and may destroy cancer cells. It is a type of monoclonal antibody.—a treatment you may be familiar with from your first-line treatment—and ibritumomabIbritumomab
A monoclonal antibody that is used in ZEVALIN.. Both are man-made antibodies.
Radiotherapy uses high-energy radiation to destroy cancer cells and shrink tumors. Radiation may come from a device outside the body (external-beam radiation therapy) or, like ZEVALIN, may come from radioactive material injected into the bloodstream.2
Different from radiation administered outside your body, ZEVALIN is delivered to certain targeted and neighboring cells in your body. ZEVALIN can affect cells up to a 5 mm radius around targeted B-cells—that's about the thickness of three pennies stacked.
ZEVALIN is delivered to certain targeted and neighboring cells in your body.
Following ZEVALIN treatment, most patients have a period of low blood cell counts. Low blood counts following treatment are common and expected, since ZEVALIN is intentionally designed to destroy certain blood cells.
Tell your doctor if you have signs or symptoms of low blood counts (eg. bleeding, easy bruising, evidence of bleeding under the skin, poor color, weakness or tiredness).
Indications and Usage
ZEVALIN® (ibritumomab tiuxetan) injection for intravenous use is a prescription medication that has three parts: two infusions of rituximab and one injection of Yttrium-90 (Y-90) ZEVALIN. Rituximab is used to reduce the number of B-cells in your blood and Y-90 ZEVALIN is given to treat your non-Hodgkin's lymphoma (NHL).
The ZEVALIN therapeutic regimen is used to treat patients with:
- Low-grade or follicular B-cell NHL that has relapsed during or after treatment with other anticancer drugs.
- Newly diagnosed follicular NHL following a response to initial anticancer therapy.
Patient Important Safety Information
What Is the Most Important Safety Information I Should Know About ZEVALIN Treatment?
The following section provides an overview of the most important safety information you should know about ZEVALIN, including side effects. Not all of the safety information about ZEVALIN treatment is included here. For complete safety information, please see the accompanying full prescribing information for ZEVALIN. Additional information may also be found on the ZEVALIN Website (www.ZEVALIN.com) or by speaking with your health care provider. Because ZEVALIN treatment includes the use of rituximab, please see the rituximab medication guide (www.rituxan.com).
WARNING: ZEVALIN TREATMENT CAN CAUSE SERIOUS SIDE EFFECTS:
- Serious Infusion Reactions: Rituximab, alone or as part of the ZEVALIN treatment, may cause serious infusion reactions. Deaths have occurred within 24 hours of rituximab infusion, an important component of the ZEVALIN treatment. Tell your doctor or infusion nurse or get medical treatment right away if you develop fever or chills, a rash, itching, dizziness, swelling of your hands, feet or face, throat irritation or trouble breathing during or after receiving the ZEVALIN treatment.
- Extended and Severe Decreases in Your Blood Counts (Cytopenias): Your doctor will monitor your blood counts after receiving the ZEVALIN treatment. Decreased blood counts can occur late and continue for more than 12 weeks after receiving ZEVALIN. Tell your doctor if you have a fever, feel too tired to do daily activities, feel weak, develop bruises or pinpoint red or purple spots on your skin, have unusual bleeding or notice blood in your urine or stool.
- Severe Skin or Mucous Membrane Reactions: If you experience any reactions related to your skin or mucous membranes (e.g. mouth, nose), your infusion of rituximab and Y-90 ZEVALIN should be discontinued.
Dosing Warning: The dose of Y-90 ZEVALIN should not exceed 32.0 mCi (1184 MBq).
Additional Safety Information:
Risk of Developing Myelodysplastic Syndrome, Leukemia and Other Malignancies (Cancers): The radiation dose resulting from therapeutic exposure to Y-90 ZEVALIN may result in secondary malignancies.
Myelodysplastic syndrome (MDS; a type of pre-cancerous bone marrow abnormality) and/or Acute Myelogenous Leukemia (AML, a type of cancer of the blood) were reported in 5.2% (11/211) of patients treated with Y-90 ZEVALIN for relapsed or refractory non-Hodgkin's lymphoma (NHL) in clinical studies, and 1.5% (8/535) of all patients included in the expanded-access trial, with median follow-up of 6.5 and 4.4 years, respectively. Among the 19 reported cases, the median time to diagnosis of MDS or AML was 1.9 years following the ZEVALIN therapy; however, the total incidence continues to increase.
Among 204 newly diagnosed patients who received Y-90 ZEVALIN, following complete or partial response to initial anticancer therapy, 7 patients (3.4%) were diagnosed with MDS/AML after receiving ZEVALIN treatment, compared to one patient (0.5%, 1/205) in the control arm, with a median follow-up of 7.3 years. Deaths due to secondary new malignancies occurred in 8 (3.9%) patients treated with ZEVALIN compared to 3 (1.5%) patients in the control arm of the study. Deaths due to MDS or AML occurred in 5 (2.5%) patients treated with ZEVALIN compared to no patients in the control arm.
- Infusion Site Leakage: ZEVALIN may leak from your vein or infusion site. Your doctor will monitor you during treatment and will stop the infusion and switch to another vein, if this occurs during treatment.
- Immunization: Do not get a vaccine that contains live virus for at least 12 months following ZEVALIN treatment.
- Precautions During and After Administration: Your doctor will discuss precautions with you to minimize radiation exposure.
- Potential for Birth Defects: ZEVALIN therapy may cause harm to an unborn baby, please tell your doctor if you are pregnant or plan to become pregnant.
- Reproductive Organs: There is a risk that ZEVALIN therapy will affect the male and female reproductive organs. Use birth control during treatment and for a minimum of 12 months following ZEVALIN therapy.
- Nursing Mothers: Discontinue nursing during and after ZEVALIN treatment.
Adverse Reactions (Side Effects): The most common adverse reactions (≥10%) in clinical trials with ZEVALIN were: decreases in blood counts, tiredness, inflammation of the nose and upper throat, nausea (upset stomach), abdominal (stomach) pain, weakness, cough, diarrhea, and fever. The most serious adverse reactions of ZEVALIN are prolonged and severe reduction in the number of blood counts and secondary cancers.
When administered following initial anticancer therapy, grade 3/4 adverse reactions of ZEVALIN include prolonged and severe decrease in blood counts (decrease in platelets [51%], decrease in neutrophils (a type of white blood cell) [41%], decrease in total white blood cells [36%], decrease in lymphocytes [18%], and decrease in red blood cells or hemoglobin [5%]), and secondary cancers (12.7%). Reductions in blood cells were more severe and more prolonged among 11 (5%) patients who received ZEVALIN after first-line fludarabine or a fludarabine-containing anticancer regimen as compared to patients receiving non-fludarabine-containing regimens. Grade 3/4 infections occurred in 8% of ZEVALIN-treated patients and in 2% of controls and included neutropenic sepsis (fever and infection due to decrease in the number of neutrophils [1%]), bronchitis, catheter sepsis (bacterial infection in the blood related to catheter), diverticulitis (inflammation in the intestines), shingles or blistering skin rash caused from herpes virus reactivation, flu, lower air passage infection, sinusitis (swelling of the sinuses), and upper air passage infection.
Grade 3/4 adverse reactions of ZEVALIN in recurring NHL patients include prolonged and severe reduction of blood cells (decrease in platelets [63%], decrease in neutrophils [60%], decrease in red blood cells or hemoglobin [17%], and ecchymosis (small blue or purple patch on the skin or mucous membrane [<1%])) and secondary cancers (5.2%). Serious infections occurred in 3% of patients (urinary tract infection, febrile neutropenia, sepsis, pneumonia, cellulitis (type of skin infection), colitis (swelling of the large intestine), diarrhea, osteomyelitis (bone infection), and upper-air passage infection). Life-threatening infections were reported in 2% of patients (sepsis, empyema (collection of pus in a cavity in the body), pneumonia, febrile neutropenia, fever, and biliary stent-associated cholangitis (bile duct infection)).
Please click here to see the full Prescribing Information, including the BOXED WARNINGS, for ZEVALIN. Because ZEVALIN treatment includes the use of rituximab, please see the rituximab medication guide (www.rituxan.com).
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
1. American Cancer Society. What is Immunotherapy? http://www.cancer.org/treatment/ treatmentsandsideeffects/treatmenttypes/immunotherapy/immunotherapy-what-is-immunotherapy. Updated March 26, 2014. Accessed May 21, 2014.
2. National Cancer Institute. NCI Dictionary of Cancer Terms. http://www.cancer.gov/dictionary. Accessed May 21, 2014.
3. ZEVALIN [package insert]. Irvine, CA: Spectrum Pharmaceuticals, Inc. 2013.
4. American Cancer Society. Monoclonal antibodies. http://www.cancer.org/treatment/ treatmentsandsideeffects/treatmenttypes/immunotherapy/immunotherapy-monoclonal-antibodies. Updated March 26, 2014. Accessed May 21, 2014.