Ibritumomab

Ibritumomab
Monoclonal antibody
TypeWhole antibody
SourceMouse
TargetCD20
Names
Pronunciation/ɪbrɪtuːmoʊmæb taɪʌksɛtæn/[1]
Trade namesZevalin
Other namesIbritumomab tiuxetan
Clinical data
Main usesNon-Hodgkin's lymphoma[2]
Side effectsLow red blood cells, low white blood cells, low platelets, weakness, fever, nausea[3]
Routes of
use		intravenous
External links
AHFS/Drugs.comMonograph
US NLMIbritumomab
Legal
License data
Legal status

Ibritumomab, sold under the trade name Zevalin, is a medication used to treat non-Hodgkin's lymphoma.[2] It is used following treatment with rituximab.[3] It is given by gradual injection into a vein.[2]

Common side effects include low red blood cells, low white blood cells, low platelets, weakness, fever, and nausea.[3] Other side effects may include Stevens-Johnson syndrome and myelodysplastic syndrome.[2] It is a monoclonal antibody attached to the radioactive element yttrium-90.[3] The monoclonal antibody binds to CD20 found on B cells.[3]

Ibritumomab was approved for medical use in the United States in 2002 and Europe in 2004.[2][3] In the United States it costs 59,300 USD for a dose as of 2021.[4] Use was not recommended by NHS Scotland in 2007 due to insufficient evidence of cost benefit.[5]

Medical use

Ibritumomab is used to treat relapsed or refractory, low grade or transformed B cell non-Hodgkin's lymphoma (NHL), a lymphoproliferative disorder, and previously untreated follicular NHL in adult patients who achieve a partial or complete response to first-line chemotherapy.[6] The treatment should not be administered to patients with ≥25% lymphoma marrow involvement and/or impaired bone marrow reserve.[7]

The treatment starts with an infusions of rituximab. This may be followed by an administration of indium-111 labelled ibritumomab tiuxetan (111In replaces the 90Y component) to allow the distribution of the drug to be imaged on a gamma camera, before the actual therapy is administered. Seven to nine days later, a second infusion of rituximab is given, followed by the 90Y-ibritumomab tiuxetan, by intravenous infusion over around 10 minutes. The radioactive activity is determined based on person's weight and platelet count.[8]

Mechanism of action

The antibody binds to the CD20 antigen found on the surface of normal and malignant B cells (but not B cell precursors), allowing radiation from the attached isotope (mostly beta emission) to kill it and some nearby cells. In addition, the antibody itself may trigger cell death via antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis. Together, these actions eliminate B cells from the body, allowing a new population of healthy B cells to develop from lymphoid stem cells.[9]

History

Developed by the IDEC Pharmaceuticals, now part of Biogen Idec,[10] ibritumomab tiuxetan was the first radioimmunotherapy drug approved by the Food and Drug Administration (FDA) in 2002 to treat cancer. It was approved for the treatment of patients with relapsed or refractory, low‑grade or follicular B‑cell non‑Hodgkin's lymphoma (NHL), including patients with rituximab refractory follicular NHL.[11] It was given marketing authorisation by the European Medicines Agency in 2004 for the treatment of adult patients with rituximab relapsed or refractory CD20+ follicular B-cell non-Hodgkin's lymphoma.[12]

In September 2009, ibritumomab received approval from the FDA for an expanded label to include previously untreated patients with a chemotherapy response.[6]

Society and culture

Availability

Ibritumomab is currently under patent protection. When first approved, it was the most expensive drug available given in a single dose, costing over US$37,000 (€30,000) for the average dose.[13][14] However, ibritumomab is essentially an entire course of lymphoma therapy which is delivered in 7–9 days, with one visit for pre-dosing rituximab, and one visit a week later for the actual ibritumomab therapeutic dose preceded by rituximab.[13]

See also

  • Tositumomab, an alternative radioimmunotherapy treatment for non-Hodgkin's lymphoma.

References

  1. ↑ "Ibritumomab Tiuxetan". National Cancer Institute. 26 February 2008. Archived from the original on 9 July 2020. Retrieved 25 July 2020.
  2. 1 2 3 4 5 "Ibritumomab Monograph for Professionals". Drugs.com. Archived from the original on 26 February 2021. Retrieved 24 November 2021.
  3. 1 2 3 4 5 6 "Zevalin". Archived from the original on 11 November 2020. Retrieved 24 November 2021.
  4. ↑ "Y-90 Zevalin Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 26 January 2021. Retrieved 24 November 2021.
  5. ↑ "ibritumomab tiuxetan (Zevalin)". Scottish Medicines Consortium. Archived from the original on 11 December 2021. Retrieved 24 November 2021.
  6. 1 2 Schaefer NG, Huang P, Buchanan JW, Wahl RL (May 2011). "Radioimmunotherapy in non-Hodgkin lymphoma: opinions of nuclear medicine physicians and radiation oncologists". Journal of Nuclear Medicine. 52 (5): 830–8. doi:10.2967/jnumed.110.085589. PMC 4380183. PMID 21536931.
  7. ↑ "Zevalin package insert" (PDF). Acrotech Biopharma. September 2019. Archived (PDF) from the original on 2021-10-07. Retrieved 2021-01-11.
  8. ↑ Tennvall, Jan; Fischer, Manfred; Bischof Delaloye, Angelika; Bombardieri, Emilio; Bodei, Lisa; Giammarile, Francesco; Lassmann, Michael; Oyen, Wim; Brans, Boudewijn (24 February 2007). "EANM procedure guideline for radio-immunotherapy for B-cell lymphoma with 90Y-radiolabelled ibritumomab tiuxetan (Zevalin)" (PDF). European Journal of Nuclear Medicine and Molecular Imaging. 34 (4): 616–622. doi:10.1007/s00259-007-0372-y. PMID 17323056. S2CID 8951564. Archived (PDF) from the original on 23 October 2020. Retrieved 11 January 2021.
  9. ↑ "Ibritumomab Tiuxetan" (PDF). US Food and Drug Administration. Archived (PDF) from the original on 2021-03-30. Retrieved 2021-01-11.
  10. ↑ Pollack, Andrew (24 June 2003). "Idec to Merge With Biogen in $6.8 Billion Deal". The New York Times. Archived from the original on 11 February 2021. Retrieved 11 January 2021.
  11. ↑ Grillo-López AJ (October 2002). "Zevalin: the first radioimmunotherapy approved for the treatment of lymphoma". Expert Review of Anticancer Therapy. 2 (5): 485–93. doi:10.1586/14737140.2.5.485. PMID 12382517. S2CID 20940701.
  12. ↑ "Zevalin". European Medicines Agency. 17 September 2018. Archived from the original on 11 November 2020. Retrieved 25 July 2020.
  13. 1 2 Cutler, Cathy S. (September 2019). "Economics of New Molecular Targeted Personalized Radiopharmaceuticals". Seminars in Nuclear Medicine. 49 (5): 450–457. doi:10.1053/j.semnuclmed.2019.07.002. PMID 31470937.
  14. ↑ Bazell, Robert (23 June 2004). "Why are the new cancer drugs so expensive?". Slate Magazine. Archived from the original on 28 May 2021. Retrieved 11 January 2021.
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