90y-Anti-Cd20 Monoclonal Antibody Therapy (Idec-Y2b8) for Recurrent B Cell Lymphoma

Knox, Susan J.; Goris, Michael L.; Becker, M.; Fowler, Sherry; Trisler, Kirk; Ning, Shoucheng; Grillo-López, Antonio J; Levy, Ronald

doi:10.1097/00002371-199408000-00059

Cited by 13 publications

(11 citation statements)

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“…We had shown in the first Phase I trial the importance of utilizing cold antibody immediately preceding the radiolabeled mAb [14,15]. The rationale is that most lymphoma patients have a sizable (but not easily quantifiable) amount of circulating CD20 antigen: normal B-cells in peripheral blood, bone marrow, liver and spleen.…”

Section: Key Data Leading Up To Product Approval Importance and Rationamentioning

confidence: 99%

“…Patients treated with Zevalin can be safely and effectively dosed based on simple body weight calculations. Other forms of RIT, particularly when radioiodine is utilized, do require patient-specific (customized) dosing, principally due to the variable and extensive excretion of the radioisotope [6,9,15,17,20].…”

Section: Clinical Efficacy Data Leading To Product Approvalmentioning

confidence: 99%

“…The most important publications for the healthcare professional involved in the treatment of the NHL patient with Zevalin are the reports on the Phase I, II and III clinical trials [14,15,18,20,23]. Equally important is the US package insert [130].…”

Section: Information Resourcesmentioning

confidence: 99%

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Zevalin: the first radioimmunotherapy approved for the treatment of lymphoma

Grillo-López¹

2002

Expert Review of Anticancer Therapy

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Conjugated antibodies have been in clinical trials for over 30 years. Immunotoxins, chemotherapy conjugates and radioimmunotherapies have been evaluated. Zevalin, the first conjugated antibody for the treatment of non-hodgkin's lymphoma (NHL) (and the first radioimmunotherapeutic for cancer) was approved by the US FDA on 19 February 2002 (approval is pending in the EEC). Zevalin (90Yttrium ibritumomab tiuxetan) has been in clinical trials since 1992. Several studies have been conducted including a randomized Phase III trial where it showed superiority to rituximab in overall response rate and in complete response rate. The current indications are: low-grade or follicular lymphoma refractory to rituximab, and relapsed or refractory, low-grade, follicular or transformed lymphoma. Additional studies have been initiated to further define the role of this new therapy in the treatment of patients with B-cell non-hodgkin's lymphoma.

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Section: Key Data Leading Up To Product Approval Importance and Rationamentioning

confidence: 99%

Section: Clinical Efficacy Data Leading To Product Approvalmentioning

confidence: 99%

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Zevalin: the first radioimmunotherapy approved for the treatment of lymphoma

Grillo-López¹

2002

Expert Review of Anticancer Therapy

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“…Yttrium-90 has no gamma emissions and hence patients who receive 90 Y therapy can be treated as outpatients. Radioimmunotherapy with Zevalin has been shown to be well tolerated and has clinically significant higher overall response rate (ORR) and complete response (CR) as compared to treatment with rituximab alone 27 28 .…”

Section: Discussionmentioning

confidence: 99%

Preparation & in vitro evaluation of⁹⁰Y-DOTA-rituximab

Kameswaran¹,

Pandey²,

Dash³

et al. 2016

Indian J Med Res

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Background & objectives:Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin's lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with 90Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent.Methods:Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice.Results:Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with 90Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP) > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with 90Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant Kd for 90Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of 90Y-DOTA-rituximab.Interpretation & conclusions:p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90Y was carried out. In vitro studies carried out in Raji cells showed the specificity of the radiolabelled conjugate suggesting the potential uitability of the formulation as a radiopharmaceutical for therapy of NHL.

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“…Da neben den Lymphomendie meistennor-malenB -Lymphozytenu nd ihreV orstufen dasC D20-Oberflächenantigene xprimieren, werdendie zirkulierendenCD20-Antigene durchzweimalige Präinfusion desunmarkierten chimärenA nti-CD20-Antikörpers Rituximab gesättigt (23).D ie Rituximab-Gabe erfolgt sieben Tage voru nd am Tage derRadioimmuntherapie selbst, unabhängig vond er Durchführung einer-Immunszintigraphie. Innerhalb vonv ier Stundenn ach derz weitenR ituximab-Infusion hatdie Gabe von 90 Y-Ibritumomab-Tiuxetan(Zevalin) zu erfolgen.…”

Section: Klinik Pretargeting Undszintigraphieunclassified

Radioimmunotherapy with yttrium-90 ibritumomab tiuxetan

Dietlein¹,

Schnell²,

Pinkert³

et al. 2005

Nuklearmedizin

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Summary 90Y-ibritumomab tiuxetan (Zevalin®) is currently approved for radioimmunotherapy of patients with relapsed or refractory follicular non-Hodgkin’s lymphoma pretreated with rituximab. Future directions are the combined use of 90Y-ibritumomab tiuxetan as part of the initial treatment and as first-line multi-agent therapy of relapsed disease. Current studies investigate patients with other than follicular indolent histologies, e. g. diffuse large cell lymphoma. Labelling of 90Y ibritumomab tiuxetan is a safe procedure, the radiochemical purity is not disturbed by a higher room temperature or by metallic impurity. Quality control is recommended by thin layer chromatography (TLC), strips >15 cm are favourable. TLC cannot distinguish between the correctly radiolabelled antibodies and radiocolloid impurity. If necessary, additional HPLC should be performed. Radiocolloid impurities are absorbed to the solid phase and do not reach the eluate. If the radiochemical purity test is insufficient (<95%), the additional cleaning using EconoPac 10 DG columns (Biorad, Hercules, CA, USA) is a reliable procedure to reduce the percentage of free radionuclide. However, this procedure is not part of the approval.

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90y-Anti-Cd20 Monoclonal Antibody Therapy (Idec-Y2b8) for Recurrent B Cell Lymphoma

Cited by 13 publications

References 0 publications

Zevalin: the first radioimmunotherapy approved for the treatment of lymphoma

Zevalin: the first radioimmunotherapy approved for the treatment of lymphoma

Preparation & in vitro evaluation of⁹⁰Y-DOTA-rituximab

Radioimmunotherapy with yttrium-90 ibritumomab tiuxetan

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90y-Anti-Cd20 Monoclonal Antibody Therapy (Idec-Y2b8) for Recurrent B Cell Lymphoma

Cited by 13 publications

References 0 publications

Zevalin: the first radioimmunotherapy approved for the treatment of lymphoma

Zevalin: the first radioimmunotherapy approved for the treatment of lymphoma

Preparation & in vitro evaluation of90Y-DOTA-rituximab

Radioimmunotherapy with yttrium-90 ibritumomab tiuxetan

Contact Info

Product

Resources

About

Preparation & in vitro evaluation of⁹⁰Y-DOTA-rituximab