Frequently Asked Questions

Can ZEVALIN be used in elderly patients?

ZEVALIN treatment has been administered in 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 NHL.1

  • In a randomized study of 414 patients with follicular NHL 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.1
  • Of 349 patients with relapsed or refractory NHL 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.1

No overall differences in safety or effectiveness of ZEVALIN treatment have been observed between elderly patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.1

Can subsequent therapies be administered after ZEVALIN treatment?

In a retrospective analysis of patients with relapsed or refractory NHL who experienced disease progression after ZEVALIN treatment and received subsequent therapy (n = 58), it was concluded that chemotherapy or autologous stem-cell transplantation (ASCT) after prior administration of ZEVALIN was feasible and reasonably well tolerated. Patients analyzed had indolent, transformed, aggressive, or mantle cell NHL (not all of which are included in the labeled indication for ZEVALIN).3*

Clinical responses were achieved when chemotherapy (e.g., CHOP, CVP/COP, purine analogs), rituximab, interferon, radiation therapy, or ASCT was administered after ZEVALIN treatment. Toxicities associated with subsequent therapies included infusion-related symptoms, grade 4 neutropenia, grade 4 thrombocytopenia, neutropenic fever, complications requiring hospitalization, and toxicities requiring the use of granulocyte colony-stimulating factor or red blood cell or platelet transfusions.4

Further analysis is needed before data can be presented on the safety and efficacy of administering subsequent therapies after ZEVALIN treatment in the first-line setting.

*As of March 2008, transformed NHL is no longer included in the labeled indication for ZEVALIN.

What incidence of infection is associated with the regimen?

When ZEVALIN was administered following first-line chemotherapy, grade 3 or 4 infections occurred in 8% of ZEVALIN-treated patients and 2% of control patients. Infections included neutropenic sepsis (1%), bronchitis, catheter sepsis, diverticulitis, herpes zoster, influenza, lower respiratory tract infection, sinusitis, and upper respiratory tract infection.1

In relapsed or refractory NHL patients, infections occurred in 29% of 349 patients during the first 3 months after initiating the ZEVALIN therapeutic regimen. Of these patients, 3% developed serious infections (e.g., urinary tract infection, febrile neutropenia, sepsis, pneumonia, cellulitis, colitis, diarrhea, osteomyelitis, and upper respiratory tract infection), and 2% developed life-threatening infections (e.g., 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).1

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

The crude incidence of treatment-related MDS/AML associated with conventional-dose chemotherapy or radiotherapy has been reported to range from 0% to 12%.5

Among 204 patients receiving ZEVLIN following first-line treatment, 2 (1%) developed acute myelogenous leukemia (AML) at approximately 2 and 3.3 years after ZEVALIN administration, respectively.1

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).1

Where is ZEVALIN administered?

ZEVALIN may be administered at any facility with an approved Radioactive Materials License (RML) and 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 Site Locator to see where ZEVALIN is offered.

Who is involved in the ZEVALIN treatment process?

Treatment with the ZEVALIN regimen involves a multidisciplinary health care team that may include the following:

  • Medical oncologist or hematologist2
  • Nuclear medicine physician or radiation oncologist2
  • Oncology or hematology nurse2
  • Nuclear medicine or radiation oncologist nurse and/or technician2
  • Nuclear pharmacist2

Cooperation between members of the multidisciplinary health care team is essential to ensure proper timing and coordination of the ZEVALIN regimen.2

ZEVALIN Support Services can assist you with your scheduling needs.

How can I obtain more information about ZEVALIN treatment?

For more information on ZEVALIN treatment, including all scientific and/or clinical questions, please contact:

ZEVALIN Support Services
1-866-298-8433

Option 1: Customer Service / Orders
Option 2: Medical Information or Adverse Events Reporting
Option 3: Product Complaints
Option 4: Reimbursement
Option 5: Rituximab Questions

ZEVALINsupport@sppirx.com

or contact ZEVALIN Medical Information

What counseling information should patients be told about the regimen?

When providing education about ZEVALIN treatment, it is important to advise patients:1

  • 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
 

References

  1. ZEVALIN [package insert]. Irvine, CA: Spectrum Pharmaceuticals, Inc.; 2011.
  2. 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. Annals of Oncology. 2005;16:786-792.
  3. Ansell SM, Ristow KM, Habermann TM, et al. Subsequent chemotherapy regimens are well tolerated after radioimmumotherapy with yttrium-90 tiuxetan for Non-Hodgkin's Lymphoma. Journal of Clinical Oncology. 2003; 20:3885-3890.
  4. Ansell SM, Schilder RJ, Pieslor PC, et al. Antilymphoma treatments given subsequent to yttrium 90 ibritumomab tiuxetan are feasible in patients with progressive Non-Hodgkin's Lymphoma: a review of the literature. Clinical Lymphoma. 2004;5:202-204.
  5. Czuczman MS, Emmanouilides C, Darif M, et al. Treatment-related myelodysplastic syndrome and acute myelogenous leukemia in patients treated with Ibritumomab Tiuxetan radioimmunotherapy. Journal of Clinical Oncology. 2007; 25:4285-4292.
 

View Indications and Important Safety Information

ZEVALIN® (ibritumomab tiuxetan) 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

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).

ADDITIONAL IMPORTANT SAFETY INFORMATION

Leukemia and Myelodysplastic Syndrome: Among 204 patients receiving Y-90-ZEVALIN following first-line chemotherapy, two patients (1%) were diagnosed with AML within 3 years of receiving ZEVALIN.

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.

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

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.

Laboratory Monitoring: Obtain complete blood counts (CBC) and platelet counts at least weekly.

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.

Creutzfeldt-Jakob Disease (CJD): The ZEVALIN therapeutic regimen contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, ZEVALIN carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of CJD also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.

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, abdominal pain, nausea, nasopharyngitis, asthenia, diarrhea, cough, and pyrexia. Common adverse reactions (≥40%) in clinical trials were: neutropenia, leukopenia, thrombocytopenia, anemia, infection, asthenia, musculoskeletal symptoms, and gastrointestinal symptoms. 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. 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. 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 read full Prescribing Information, including BOXED WARNINGS, for ZEVALIN. Because the ZEVALIN therapeutic regimen includes the use of rituximab, please also consult prescribing information for rituximab.