Ibritumomab tiuxetan

Compound Name:Ibritumomab tiuxetanMolecular Target:CD20Molecular Structure:murine IgG1? monoclonal antibody, conjugated to a chelator (tiuxetan) for labeling with Indium-111 or Yttrium-90Licensed Indication:non-Hodgkins Lymphoma (CD20 positive, low-grade or follicular) which is relapsed or refractory to rituximab, in combination with rituximabManufacturer and/or Distributor:Cell Therapeutics; Biogen IdecInitial FDA Approval2002SummaryIbrutumomab tiuxetan (Zevalin) is an immunoconjugate of an IgG1κ murine monoclonal antibody that targets the B-cell CD20 surface antigen. It is covalently bound to the linker-chelator tiuxetan that binds to radioisotopes, thus delivering the radiation to the lymphoma B cells. It is approved for use in conjunction with two doses of rituximab spaced about 1 week apart, and it is given within 4 hours of the second rituximab dose. Immediately before use, ibritumomab tiuxetan is conjugated to Yttrium-90, which is a beta emitter with a half-life of 2.67 days. Ibritumomab tiuxetan was first approved by the FDA in 2002 for the treatment of CD20 positive, relapsed or refractory, low-grade or follicular B-cell non-Hodgkin’s lymphoma (NHL), including patients previously treated with rituximab. A current additional indication is previously untreated follicular NHL patients who have achieved a partial or complete response to first-line chemotherapy. In 2011, the drug’s labeling was modified to remove the requirement to precede the therapeutic administration of ibritumomab tiuxetan bound to Yttrium-90 with radioscan imaging with ibritumomab tiuxetan bound to In-111. In relapsed or refractory patients, ibritumomab tiuxetan was more effective (80% response) than rituximab (56%). However, per National Comprehensive Cancer Network’s Drugs & Biologics Compendium (2015), diffuse large B-cell non-Hodgkin lymphoma is not a recommended indication of ibritumomab tiuxetan. Serious reactions to the ibritumomab tiuxetan therapeutic regimen include fatal infusion reactions to rituximab; severe and prolonged cytopenias (in most patients); severe cutaneous and mucocutaneous reactions; and the development of leukemia or myelodysplastic syndrome. Because of these concerns, the Zevalin therapeutic regimen is only approved by the FDA for patients who have failed other treatments.References

Package Insert: Revised: 8/2013

Updated information: May 2014

1. Witzig TE, Flinn IW, Gordon LI, Emmanouilides C, Czuczman MS, Saleh MN, et al. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma. J Clin Oncol. 2002 Aug 1;20(15):3262-3269. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12149300

2. Czuczman MS, Emmanouilides C, Darif M, Witzig TE, Gordon LI, Revell S, et al. Treatment-related myelodysplastic syndrome and acute myelogenous leukemia in patients treated with ibritumomab tiuxetan radioimmunotherapy. J Clin Oncol. 2007 Sep 20;25(27):4285-4292. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17709799

3. Witzig TE, Molina A, Gordon LI, Emmanouilides C, Schilder RJ, Flinn IW, et al. Long-term responses in patients with recurring or refractory B-cell non-Hodgkin lymphoma treated with yttrium 90 ibritumomab tiuxetan. Cancer. 2007 May 1;109(9):1804-1810. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17380530

4. Emmanouilides C. Review of Y-ibritumomab tiuxetan as first-line consolidation radio-immunotherapy for B-cell follicular non-Hodgkin's lymphoma. Cancer Manag Res. 2009;1:131-136. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21188131

5. Hohloch K, Zinzani PL, Linkesch W, Jurczak W, Deptala A, Lorsbach M, et al. Radioimmunotherapy with (90)Y-ibritumomab tiuxetan is a safe and efficient treatment for patients with B-cell lymphoma relapsed after auto-SCT: an analysis of the international RIT-Network. Bone Marrow Transplant. 2011 Jun;46(6):901-903. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20871640

6. Sánchez Ruiz AC, de la Cruz-Merino L, Provencio Pulla M. Role of consolidation with yttrium-90 ibritumomab tiuxetan in patients with advanced-stage follicular lymphoma. Ther Adv Hematol. 2014 Jun;5(3):78-90. http://www.ncbi.nlm.nih.gov/pubmed/24883180

7. Arnason JE, Luptakova K, Rosenblatt J, Tzachanis D, Avigan D et al. Yttrium-90 ibritumomab tiuxetan followed by rituximab maintenance as treatment for patients with diffuse large B-cell lymphoma are not candidates for autologous stem cell transplant. Acta Haematol. 2015;133(4):347-53. http://www.ncbi.nlm.nih.gov/pubmed/25677780

8. National Comprehensive Cancer Network. Drugs & Biologics Compendium. Ibritumomab tiuxetan. 2015. NCCN: Fort Washington, PA. http://www.nccn.org/professionals/drug_compendium/content/contents.asp

9. Rizzieri D. Zevalin(®) (ibritumomab tiuxetan):After more than a decade of treatment experience, what have we learned? Crit Rev Oncol Hematol. 2016;(105):5-17. https://www.ncbi.nlm.nih.gov/pubmed/27497027