ZEVALIN logo ZEVALIN Important Safety Information ZEVALIN Full Prescribing Information ZEVALIN Treatment Site Locator ZEVALIN Patient site

This section is intended for U.S. Healthcare Professionals only

 

Frequently Asked Questions

Sign up to become a ZEVALIN treatment facility

Can ZEVALIN be used in elderly patients?

ZEVALIN treatment has been administered in registrational clinical studies to elderly patients aged 65 years and older, including patients aged 75 years and older, for previously untreated and relapsed or refractory follicular non-Hodgkin’s lymphoma.1

  • In a randomized study of 414 patients with follicular non-Hodgkin’s lymphoma who had a response to first-line chemotherapy, 206 patients received ZEVALIN. Of these patients 14% (29 patients) were 65 years and over, while 2% (4 patients) were 75 years and older.
  • In the control arm, 10% (21 patients) were 65 years or over and 0% (0 patients) were 75 years or older. Of 349 patients with relapsed or refractory non-Hodgkin’s lymphoma treated with the ZEVALIN therapeutic regimen in clinical studies, 38% (132 patients) were age 65 years and over, while 12% (41 patients) were age 75 years and over.

No overall differences in safety or effectiveness of ZEVALIN treatment were observed between elderly patients and younger patients in these studies, but greater sensitivity of some older individuals cannot be ruled out.

Why was the administration of Indium-111 and the bioscan requirement removed from the label?

In November 2011, the FDA approved removing the Indium-111 imaging dose and the bioscan requirement that were previously part of the ZEVALIN treatment regimen. This was based on further analysis of clinical studies and post-marketing surveillance:

  • At ZEVALIN approval, an Indium-111 (In-111) imaging dose and bioscan was required prior to Y-90 ZEVALIN treatment based on risk of end-organ damage caused by altered bio-distribution2
  • Analysis of data in 253 patients showed that the In-111 imaging dose and bioscan was not a reliable predictor of altered Y-90 ZEVALIN bio-distribution2
    • 4.3% of patients were suspected to have altered bio-distribution
    • 1.3% of patients were true positives based on expert review
    • 3% of patients were found to be false positives based on expert review
  • Global post-marketing surveillance showed no additional safety risk in patients treated with ZEVALIN without the In-111 imaging dose and bioscan2
    • From 2002-2010, approximately 16,000 patients worldwide received ZEVALIN in routine clinical practice
      • ~ 9,000 in countries with the Indium-111 bioscan requirement
      • ~ 7,000 in countries WITHOUT the Indium-111 bioscan requirement
  • Overall incidence of serious anaphylactoid reactions were similar in regions that do and do not require the Indium-111bioscan (0.4% in both groups)
  • Overall incidence of bone marrow failure were similar in regions that do and do not require the Indium-111bioscan (3.3% vs. 3.8%)

What was the basis for the original Indium-111 Ibritumomab tiuxetan requirement?

  • At ZEVALIN approval in the U.S., an Indium-111 (Indium-111) bioscan was required prior to Y-90 ZEVALIN treatment based on the risk of unintended end-organ damage caused by altered Y-90 ZEVALIN bio-distribution
  • Only 2 other countries (Switzerland and Japan) have the same Indium-111 bioscan requirement
  • 42 other countries approved ZEVALIN without the Indium-111 bioscan

What is the ZEVALIN treatment regimen?

Visit the ZEVALIN Dosing and Administration page to learn more.

What incidence of infection is associated with the regimen?

In relapsed or refractory NHL patients, infections occurred in 29% of 349 patients during the first 3 months after initiating the ZEVALIN therapeutic regimen and 3% developed serious infections (urinary tract infection, febrile neutropenia, sepsis, pneumonia, cellulitis, colitis, diarrhea, osteomyelitis, and upper respiratory tract infection). Life-threatening infections were reported in 2% (sepsis, empyema, pneumonia, febrile neutropenia, fever and biliary stent-associated cholangitis). From 3 months to 4 years after ZEVALIN treatment, 6% of patients developed infections; 2% were serious (urinary tract infection, bacterial or viral pneumonia, febrile neutropenia, perihilar infiltrate, pericarditis, and intravenous drug-associated viral hepatitis) and 1% were life-threatening infections (bacterial pneumonia, respiratory disease, and sepsis). When administered following first-line chemotherapy, Grade 3-4 infections occurred in 8% of ZEVALIN treated patients and in 2% of controls and included neutropenic sepsis (1%), bronchitis, catheter sepsis, diverticulitis, herpes zoster, influenza, lower respiratory tract infection, sinusitis, and upper respiratory tract infection.

What is the incidence of acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) following administration of the regimen?

Among 746 patients with relapsed/refractory NHL, 19 (2.6%) patients developed MDS/AML with a median follow-up of 4.4 years. The overall incidence of MDS/AML among the 211 patients included in the clinical studies was 5.2% (11/211), with a median follow-up of 6.5 years and median time to development of MDS/AML of 2.9 years. The cumulative Kaplan-Meier estimated incidence of MDS/secondary leukemia in this patient population was 2.2% at 2 years and 5.9% at 5 years. The incidence of MDS/AML among the 535 patients in the expanded access programs was 1.5% (8/535) with a median follow-up of 4.4 years and median time to development of MDS/AML of 1.5 years. Multiple cytogenetic abnormalities were described, most commonly involving chromosomes 5 and/or 7. The risk of MDS/AML was not associated with the number of prior treatments (0-1 versus 2-10). Among 204 patients receiving Y-90-ZEVALIN following first-line treatment, 7 (3%) patients developed MDS/AML between approximately 2 to 7 years after ZEVALIN administration

Where is ZEVALIN administered?

ZEVALIN may be administered at any facility with an approved Radioactive Materials License (RML) and one or more authorized user physicians. For a listing of treatment centers that administer ZEVALIN, please call ZEVALIN Support Services at 1-866-298-8433 or use our ZEVALIN Administration Facility Locator to see where ZEVALIN is administered. Only administer rituximab/ZEVALIN in facilities where immediate access to resuscitative measures is available.

Who is involved in the ZEVALIN treatment process?

Treatment with the ZEVALIN regimen involves a multidisciplinary health care team that may include one or more of the following:3

  • Medical oncologist or hematologist
  • Nuclear medicine physician or radiation oncologist
  • Oncology or hematology nurse
  • Nuclear medicine or radiation oncologist nurse and/or technician
  • Nuclear pharmacist

Cooperation between members of the multidisciplinary health care team is essential to ensure proper timing and coordination of the ZEVALIN regimen. ZEVALIN Support Services can assist you with your scheduling needs.


What counseling information should you tell your patients about the regimen?

When providing education about ZEVALIN treatment, it is important to advise patients:

  • To contact a health care professional for severe signs and symptoms of infusion reactions
  • To take premedications as prescribed
  • To report any signs or symptoms of cytopenias (e.g., bleeding, easy bruising, petechiae or purpura, pallor, weakness, or fatigue)
  • To avoid medications that interfere with platelet function, except as directed by a health care professional
  • To seek prompt medical evaluation for diffuse rash, bullae, or desquamation of the skin or oral mucosa
  • To immediately report symptoms of infection (e.g., pyrexia)
  • That immunization with live viral vaccines is not recommended for 12 months following the ZEVALIN therapeutic regimen
  • To use effective contraceptive methods during treatment and for a minimum of 12 months following ZEVALIN therapy
  • To discontinue nursing during and after ZEVALIN treatment

Indications and Usage

ZEVALIN® is a CD20-directed radiotherapeutic antibody administered as part of the ZEVALIN therapeutic regimen indicated for the treatment of patients with:

  • Relapsed or refractory, low-grade or follicular B-cell non-Hodgkin’s lymphoma (NHL).
  • Previously untreated follicular NHL who achieve a partial or complete response to first-line chemotherapy.

Important Safety Information

WARNING: SERIOUS INFUSION REACTIONS, PROLONGED AND SEVERE CYTOPENIAS, and SEVERE CUTANEOUS
AND MUCOCUTANEOUS REACTIONS

Serious Infusion Reactions: Deaths have occurred within 24 hours of rituximab infusion, an essential component of the ZEVALIN therapeutic regimen. These fatalities were associated with hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock. Most (80%) fatalities occurred with the first rituximab infusion. Discontinue rituximab and Y-90 ZEVALIN infusions in patients who develop severe infusion reactions.

Prolonged and Severe Cytopenias: Y-90 ZEVALIN administration results in severe and prolonged cytopenias in most patients. Do not administer Y-90 ZEVALIN to patients with ≥25% lymphoma marrow involvement and/or impaired bone marrow reserve.

Severe Cutaneous and Mucocutaneous Reactions: Severe cutaneous and mucocutaneous reactions, some fatal, can occur with the ZEVALIN therapeutic regimen. Discontinue rituximab and Y-90 ZEVALIN infusions in patients experiencing severe cutaneous or mucocutaneous reactions.

Dosing: The dose of Y-90 ZEVALIN should not exceed 32.0 mCi (1184 MBq).

Risk of Developing Myelodysplastic Syndrome, Leukemia and Other Malignancies: The radiation dose resulting from therapeutic exposure to Y-90 radiolabeled ZEVALIN may result in secondary malignancies.

Myelodysplastic syndrome (MDS) and/or acute myelogenous leukemia (AML) were reported in 5.2% (11/211) of patients with relapsed or refractory NHL enrolled in clinical studies and 1.5% (8/535) of 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 treatment with the ZEVALIN therapeutic regimen; however, the cumulative incidence continues to increase.

Among 204 patients receiving Y-90-ZEVALIN following first-line chemotherapy, 26 (12.7%) patients in the ZEVALIN arm developed a second primary malignancy compared to 14 (6.8%) of patients in the control arm. Seven patients (3.4%, 7/204) were diagnosed with MDS/AML after receiving ZEVALIN, compared to one patient (0.5%, 1/205) in the control arm, with a median follow-up of 7.3 years. Deaths due to second primary malignancy included 8 (3.9%) patients in the ZEVALIN arm compared to 3 (1.5%) patients in the control arm. Deaths due to MDS/AML included five (2.5%) patients in the ZEVALIN arm compared to no patients in the control arm.

Extravasation: Monitor for extravasation and terminate infusion if it occurs. Resume infusion in another limb.

Immunization: Do not administer live viral vaccines to patients who recently received ZEVALIN.

Radionuclide Precautions: During and after radiolabeling ZEVALIN with Y-90, minimize radiation exposure to patients and to medical personnel, consistent with institutional good radiation safety practices and patient management procedures.

Embryo-fetal Toxicity: May cause fetal harm if given during pregnancy.

Impairment of Fertility: There is a potential risk that the ZEVALIN therapeutic regimen could cause toxic effects on the male and female gonads. Effective contraceptive methods should be used during treatment and for up to 12 months following the ZEVALIN therapeutic regimen.

Nursing Mothers: Patients should be advised to discontinue nursing during and after ZEVALIN treatment.

Adverse Reactions: The most common adverse reactions of ZEVALIN are cytopenias, fatigue, nasopharyngitis, nausea, abdominal pain, asthenia, cough, diarrhea, and pyrexia. Common adverse reactions (≥10%) in clinical trials were: cytopenias, fatigue, nasopharyngitis, nausea, abdominal pain, asthenia, cough, diarrhea, and pyrexia. The most serious adverse reactions of ZEVALIN are prolonged and severe cytopenias (thrombocytopenia, anemia, lymphopenia, neutropenia) and secondary malignancies.

When administered following first-line chemotherapy, grade 3/4 adverse reactions of ZEVALIN include prolonged and severe cytopenias (thrombocytopenia [51%], neutropenia [41%], leukopenia [36%], lymphopenia [18%], and anemia [5%]) and secondary malignancies (12.7%). Cytopenias were more severe and more prolonged among eleven (5%) patients who received ZEVALIN after first-line fludarabine or a fludarabine-containing chemotherapy 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 (1%), bronchitis, catheter sepsis, diverticulitis, herpes zoster, influenza, lower respiratory tract infection, sinusitis, and upper respiratory tract infection.

Grade 3/4 adverse reactions of ZEVALIN in relapsed or refractory NHL patients include prolonged and severe cytopenias (thrombocytopenia [63%], neutropenia [60%], anemia [17%], and ecchymosis [<1%]) and secondary malignancies (5.2%). Serious infections occurred in 3% of patients (urinary tract infection, febrile neutropenia, sepsis, pneumonia, cellulitis, colitis, diarrhea, osteomyelitis, and upper respiratory tract infection). Life-threatening infections were reported in 2% of patients (sepsis, empyema, pneumonia, febrile neutropenia, fever, and biliary stent-associated cholangitis).

Please click here to see the full Prescribing Information, including the BOXED WARNINGS, for ZEVALIN. Because the ZEVALIN therapeutic regimen includes the use of rituximab, please also consult Prescribing Information for rituximab (www.rituxan.com).

ISI-0154-079503

References:

1. ZEVALIN [package insert]. Irvine, CA: Spectrum Pharmaceuticals, Inc. 2013.

2. BLA 125019/194 supplement, dated January 20, 2011 (eCTD Sequence 0276)

3. Hagenbeek A, Lewington V. Report of a European consensus workshop to develop recommendations for the optimal use of (90)Y-ibritumomab tiuxetan (ZEVALIN) in lymphoma. Ann Oncol. 2005;16:786-792.

Back to top