Zevalin: 90yttrium labeled anti-CD20 (ibritumomab tiuxetan), a new treatment for non-Hodgkin's lymphoma.
Zevalin (ibritumomab tiuxetan, IDEC-Y2B8) is a murine IgG1 kappa monoclonal antibody conjugated to tiuxetan (MXDTPA) that chelates Yttrium or Indium and is directed against the CD 20 molecules of B lymphocytes. Phase I studies have determined the optimal dose of pretreatment rituximab to be 250 mg/m2 seven days prior and immediately prior to the administration of Zevalin. Phase I/II data have determined the dose of 0.4 mCi/kg to be the maximum tolerated dose (MTD) for patients with platelet counts > 150,000 and < 25% bone marrow involvement with NHL. The dose of 0.3 mCi/kg is the MTD in patients with platelet counts between 100,000-149,000. Toxicity is primarily hematologic, transient, and reversible. Dosimetry has been completed using 111In-2B8. Results to date demonstrate that, at the above doses, no patients exceeded the protocol-prescribed organ maximum dose of 2,000 cGy or red marrow maximum dose of 300 cGy. Therefore, future use will not require pretreatment dosimetry. Zevalin contains a pure beta-emitting isotope; no protective patient or staff isolation procedures are required. A randomized Phase III trial has been completed, comparing Zevalin with a standard dose of rituximab (375 mg/m2 q week for four weeks) in patients with relapsed indolent or follicular transformed NHL. The overall response rate (ORR) was 80% in the Zevalin arm compared to 56% (p = 0.002) in the rituximab arm. The CR was 30% vs. 16% (p=0.04). A nonrandomized trial in patients refractory to rituximab demonstrated an ORR of 74% and a CR rate of 15%. A Phase II study of a reduced dose of Zevalin in patients with mild thrombocytopenia demonstrated an ORR of 67% and a 33% CR rate. Zevalin is safe and effective in patients with relapsed or refractory NHL, even in patients refractory to prior rituximab therapy.
Krasner
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Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA 02115, USA.
Joyce
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology / Q000628:therapy*; D015021:Yttrium Radioisotopes
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D015021:Yttrium Radioisotopes; C422802:ibritumomab tiuxetan