Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A high-affinity IgG1 kappa murine monoclonal anti-CD20 antibody (IDEC-2B8) was developed for radioimmunotherapy of non-Hodgkin's B-cell lymphoma. A stable immunoconjugate (Zevalintrade mark) was prepared by reacting IDEC-2B8 with a derivative of diethylenetriaminepentaacetic acid, designated MX-DTPA, a chelator exhibiting high affinity and retention for 90Y. Zevalin exhibited antigen specificity, human tissue reactivity, and preclinical safety profile comparable to the native antibody. The conjugate radiolabeled with 90Y (90Y-Zevalin) or 111In (111In-Zevalin) exhibited excellent retention of immunoreactivity with radioincorporations >95%. The radiolabeled conjugates formulated in PBS containing human serum albumin were stable in vitro at 4 degrees C for 48 h as indicated by negligible loss of radioisotope and retention of binding to CD20+ cells. In vitro human serum stability studies at 37 degrees C with 90Y-Zevalin indicated that loss of 90Y from the conjugate was minimal, averaging 1% per day. Biodistribution studies in BALB/c mice confirmed the in vitro stability of 90Y-Zevalin and 111In-Zevalin. In particular, excellent in vivo retention of 90Y by the conjugate was demonstrated by minimal bone accumulation (</=3% of the injected dose over three days). Radiation dose estimates to normal organs calculated from mouse biodistribution studies with 90Y-Zevalin were comparable to those determined in a phase I/II clinical trial and below generally accepted safe radiation levels. Studies in athymic mice bearing CD20+ tumors demonstrated that 111In-Zevalin accumulated in the tumors preferentially compared with normal organs. 90Y-Zevalin is currently being evaluated in phase III clinical trials for treatment of relapsed or refractory low-grade, follicular or transformed B-cell non-Hodgkin's lymphoma.
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PMID:Preclinical evaluation of 90Y-labeled anti-CD20 monoclonal antibody for treatment of non-Hodgkin's lymphoma. 1053 87

Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA) is a monoclonal antibody that targets the CD20 antigen present in most B-cell non-Hodgkin's lymphomas. Previous studies have shown overall response rates (ORR) of approximately 50% in relapsed patients. Ibritumomab is the murine parent anti-CD20 antibody that is linked through a MX-DTPA chelator to yttrium 90 (90Y) to form the radioimmunoconjugate 90Y-ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals, San Diego, CA). A phase I study of 90Y-ibritumomab tiuxetan determined that 0.4 mCi/kg was the maximum tolerated dose, and responses were reported in 67% of all patients and in 82% of patients with low-grade non-Hodgkin's lymphoma. A separate trial randomized eligible patients to either rituximab or 90Y-ibritumomab tiuxetan. An interim analysis of the first 90 patients showed an ORR of 80% with 90Y-ibritumomab tiuxetan versus 44% with rituximab (P < .05). A subsequent trial for patients with rituximab-refractory disease showed a 46% ORR. These studies show that 90Y-ibritumomab tiuxetan is an active agent in relapsed non-Hodgkin's lymphoma and appears to have a higher ORR compared with unconjugated rituximab.
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PMID:The use of ibritumomab tiuxetan radioimmunotherapy for patients with relapsed B-cell non-Hodgkin's lymphoma. 1122 3

Clinical trials of an yttrium-90 (90Y)-conjugated monoclonal antibody to CD20 in patients with relapsed B cell non-Hodgkin lymphoma (NHL) are reviewed. Ibritumomab is the murine parent anti-CD20 antibody engineered to make the human chimeric antibody rituximab. Tiuxetan is an MX-DTPA linker chelator attached to ibritumomab to form ibritumomab tiuxetan (Zevalin). Ibritumomab tiuxetan can react with indium-111 (111In) or 90Y to form 111In-ibritumomab tiuxetan, which is used for dosimetry, or 90Y-ibritumomab tiuxetan, which is used for therapy of B cell NHL. In this report, the results of five separate clinical trials of ibritumomab tiuxetan are reviewed. Two phase I trials of 90Y-ibritumomab tiuxetan were performed, one using cold ibritumomab prior to 90Y-ibritumomab tiuxetan, and one using rituximab prior to 90Y-ibritumomab tiuxetan. The optimal schedule was found to be rituximab on days I and 8, and 90Y-ibritumomab tiuxetan 0.4 mCi/kg i.v. on day 8; no stem cells or prophylactic growth factors were used. A dose of 0.3 mCi/kg was recommended for patients with a baseline platelet count of 100,000-149,000x10(6)/l. The only significant toxicity was reversible myelosuppression. With this schedule, the overall response rate (ORR) was 67% of all patients and 82% of those with low-grade NHL. The phase I/II trials were followed by a phase III trial that randomized 143 eligible patients to either rituximab or 90Y-ibritumomab tiuxetan radioimmunoconjugate to demonstrate that the combination of the 90Y radioisotope to the murine anti-CD20 antibody provided additional efficacy over the unconjugated ("cold") rituximab alone. A planned interim analysis of the first 90 patients demonstrated an ORR of 80% with 90Y-ibritumomab tiuxetan vs 44% for rituximab (P < 0.05). To provide additional evidence of the benefit of 90Y radioimmunotherapy over rituximab immunotherapy, patients who were nonresponsive or refractory to rituximab were enrolled in an additional trial and treated with 90Y-ibritumomab tiuxetan 0.4 mCi/kg. An ORR of 46% was achieved in these rituximab-refractory patients. These results provide further evidence of the added value of 90Y. Therefore 90Y-ibritumomab tiuxetan radioimmunotherapy is a useful new treatment modality for patients with B cell NHL. Future trials are needed to define the optimal time in the disease course when this modality should be used.
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PMID:Radioimmunotherapy for patients with relapsed B-cell non-Hodgkin lymphoma. 1158 75

Immunotherapy with the anti-CD20 monoclonal antibody rituximab has been shown in clinical trials to be effective in the treatment of both indolent and aggressive non-Hodgkin's lymphomas (NHL). Recent studies have demonstrated improved clinical benefit with extended dose and maintenance therapies in patients with indolent lymphomas and chronic lymphocytic leukemia. Rituximab's label was recently expanded to include treatment of bulky disease, retreatment of patients previously treated with rituximab, and an eight-week extended treatment schedule. Rituximab has also been effectively combined with chemotherapy, resulting in higher response rates and longer response durations in randomized trials in patients with aggressive lymphoma. Studies continue to evaluate and expand the role of rituximab in the treatment of NHL, including its use in combined immunotherapy approaches and autologous stem cell transplant as well as in the treatment of autoimmune disorders. Radioimmunotherapy with the rituximab and ibritumomab tiuxetan (Zevalin) regimen was recently approved for the treatment of relapsed or refractory low-grade, follicular or CD20+ transformed NHL, including rituximab refractory follicular NHL. The regimen is delivered on an outpatient basis over the course of a week. Studies are currently exploring sequential dose therapy, radioimmunotherapy with rituximab maintenance, and ibritumomab tiuxetan radioimmunotherapy as part of autologous stem cell transplant. Current understanding of the mechanisms of action of rituximab and the use of rituximab and ibritumomab tiuxetan in patients with indolent and aggressive NHL will be discussed.
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PMID:Rituxan immunotherapy and zevalin radioimmunotherapy in the treatment of non-Hodgkin's lymphoma. 1452 25

We previously demonstrated that yttrium-90 (Y-90) ibritumomab tiuxetan (Zevalin) radioimmunotherapy (RIT) was safe and effective for relapsed or refractory CD20(+), B-cell, non-Hodgkin lymphoma (NHL). We now provide long-term follow-up data in responding patients based on International Workshop Response Criteria. Complete (CR), CR unconfirmed (CRu), and partial response (PR) rates were 29%, 22%, and 22%, respectively (overall response rate 73%, 51% in CR/CRu). Mean time to progression (TTP) and duration of response (DR) in responders were 12.6 months and 11.7 months, respectively. At the maximum tolerated dose (0.4 mCi/kg [14.8 MBq/kg]), TTP and DR in complete responders (CR/CRu) were 28.3 and 27.5 months, respectively. Nine patients (24% of responding patients) had a TTP of more than 3 years. Long-term responders (> 5 years) have been identified. Ibritumomab tiuxetan produces durable responses in patients with indolent and diffuse large B-cell lymphoma.
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PMID:Durable responses after ibritumomab tiuxetan radioimmunotherapy for CD20+ B-cell lymphoma: long-term follow-up of a phase 1/2 study. 1501 44

This article will review the clinical development of ibritumomab tiuxetan, a yttrium-90-conjugated monoclonal antibody to CD20, for patients with relapsed B-cell non-Hodgkin's lymphomas. Ibritumomab is the murine parent anti-CD20 antibody that was engineered to make the human chimeric antibody rituximab. Tiuxetan is an MX-DTPA chelator that is linked to ibritumomab to form ibritumomab tiuxetan. Since yttrium-90 ((90)Y) is a pure beta emitter and cannot be used for patient imaging, indium-111 ((111)In) is chelated to ibritumomab tiuxetan for tumor and normal organ imaging in clinical practice and for dosimetry in clinical trials. (90)Y-ibritumomab tiuxetan is the form used for therapy. This review discusses the clinical trials that have demonstrated the efficacy of ibritumomab tiuxetan and summarizes the safety data in patients with relapsed B-cell non-Hodgkin's lymphomas. Two phase I trials of (90)Y-ibritumomab tiuxetan were conducted to establish the toxicity profile and the maximum tolerated single dose that could be administered to outpatients without the use of stem cells or prophylactic growth factors. In the first trial, cold ibritumomab was used prior to ibritumomab tiuxetan; the second trial used the human chimeric antibody rituximab. The phase I trials determined that in patients with a platelet count of greater than or equal to 150 x 10(9)/l, a schedule of intravenous rituximab 250 mg/m(2) on days 1 and 8, and 0.4 mCi/ kg of intravenous (90)Y-ibritumomab tiuxetan on day 8 was safe and efficacious and did not require stem cells. A dose of 0.3 mCi/kg was recommended for patients with a baseline platelet count of 100,000- 149,000 x 10(6)/l. Adverse events were primarily hematologic, and nonhematologic adverse events were primarily due to rituximab. There was no normal organ toxicity. The overall response rate was 67% for all patients and 82% in patients with low-grade non-Hodgkin's lymphomas. A subsequent phase III trial randomized 143 eligible patients to either rituximab or ibritumomab tiuxetan. The aim was to demonstrate that the addition of the yttrium-90 radioisotope to the antibody provided additional efficacy over the unconjugated ("cold") rituximab alone. The results of this study showed an overall response rate of 80% with (90)Y-ibritumomab tiuxetan versus 56% for rituximab (p = 0.002). An additional trial enrolled 54 patients who were nonresponsive or refractory to rituximab and treated the patients with a single dose of 0.4 mCi/kg (90)Y-ibritumomab tiuxetan. An overall response rate of 74% was found in these rituximab-refractory patients. These data provide further evidence of the added value of the yttrium-90. Finally, a fifth trial treated 30 patients with mild thrombocytopenia using 0.3 mCi/kg (90)Y-ibritumomab tiuxetan and found an overall response rate of 83%. (90)Y-ibritumomab tiuxetan radioimmunotherapy is a new treatment modality for patients with relapsed B-cell non-Hodgkin's lymphoma. The advantages of this therapy are that it utilizes targeted radiation in a single-dose, outpatient schedule that is well tolerated and accepted by the patient. Future trials will build on these results and determine at what point in the disease course this modality can best be utilized to maximize the benefits to the patient.
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PMID:Yttrium-90-ibritumomab tiuxetan radioimmunotherapy: a new treatment approach for B-cell non-Hodgkin's lymphoma. 1504 33

Yttrium-90 ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals Corp., San Diego, CA) is the first radioimmunotherapy agent approved by the U.S. Food and Drug Administration (FDA) for treatment of non-Hodgkin lymphoma. In a randomized clinical trial comparing Zevalin with rituximab, the overall response rate was 80% and 56%, respectively. Response was determined by assessing the size of lymph nodes on CT scans. FDG PET has been well accepted as an accurate imaging study for staging non-Hodgkin lymphoma and evaluating response to treatment. Simultaneous FDG PET and CT imaging (PET CT) provides coregistered functional PET images with anatomic CT images. We describe 2 cases of non-Hodgkin lymphoma treated in which response was followed using PET CT.
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PMID:FDG PET CT assessment of treatment response after yttrium-90 ibritumomab tiuxetan radioimmunotherapy. 1602 58

Relapse continues to be the primary cause of treatment failure in patients with non-Hodgkin's lymphomas (NHL) undergoing high-dose therapy and autologous stem cell transplantation. The anti-CD20 radioimmunoconjugates, Y-90 ibritumomab tiuxetan (Zevalin; Biogen Idec, Inc., Cambridge, MA, USA) and I-131 tositumomab (Bexxar; Corixa, Seattle, WA; and Glaxo Smith Kline; Philadelphia, PA, USA) have been associated with high response rates, durable remissions and limited toxicity apart from myelosuppression, making them ideal candidates for use in autotransplantation. Tested first as single agents in relapsed patients with indolent and transformed NHL, and then at much higher doses with stem cell support, these agents have now been combined with high-dose chemotherapy prior to autologous stem cell transplant. Radioimmunoconjugates have been used to replace total body irradiation (TBI) in some studies and to augment standard chemotherapy regimens in others. Thus far the results are promising, with combinations of radioimmunoconjugates and chemotherapy producing long-lasting responses in high-risk patients with no more toxicity than that caused by standard conditioning regimens. These results are notable in light of the fact that the dose of radiation delivered to the tumor is 10-fold higher than the dose achievable with TBI. Whether this increase in radiation dose to the targeted lymphoma translates into more durable remissions and an improvement in overall survival requires further investigation.
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PMID:Radioimmunotherapy and autologous stem cell transplantation for the treatment of B-cell lymphomas. 1643 79

Radioimmunotherapy (RIT) with Yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin) combines the tumor targeting attributes of a monoclonal antibody against the CD20 antigen and the pure beta-radiation of 90Y. High efficacy and a favorable safety profile have been demonstrated in Phase II and III clinical trials enrolling patients with CD20+ B-cell non-Hodgkin lymphoma (B-NHL). On the basis of these results, 90Y-ibritumomab tiuxetan was approved in the United States for the treatment of patients with follicular lymphoma (FL) or transformed B-NHL. In the European Union its use was restricted to FL, refractory to or relapsed after rituximab. There are a number of important clinical trials currently evaluating 90Y-ibritumomab tiuxetan in other subtypes of lymphoma such as diffuse large-cell and mantle-cell lymphoma, as consolidation therapy or as part of myeloablative regimens. In light of the constantly increasing clinical experience with RIT, clinicians face the challenge of how to best integrate this promising new treatment option into existing established treatment algorithms. By incorporating the most recent data in this rapidly developing field, this review article focuses on current recommendations for the use of 90Y-ibritumomab tiuxetan in patients with malignant lymphoma, outlines future perspectives, and provides practical recommendations for patient management.
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PMID:Recommendations for the use of yttrium-90 ibritumomab tiuxetan in malignant lymphoma. 1682 93

Radioimmunotherapy (RIT) combines the targeting advantage of a monoclonal antibody with the radiosensitivity of non-Hodgkin lymphoma (NHL) cells. There are now two radioimmunoconjugates (RICs) - ibritumomab tiuxetan (Zevalin) and tositumomab (Bexxar) - that are approved by the FDA in the US for relapsed low-grade or follicular B-cell NHL. Both agents target the CD20 antigen on B-cell lymphoma cells. In relapsed disease, single doses of RIT produce an 80% overall response rate, with approximately 20% of patients achieving durable responses. RIT is very well tolerated and is delivered on an outpatient basis over 1 week. The only significant toxicity is reversible myelosuppression. Both RIT agents have demonstrated high anti-tumor activity in patients who are refractory to rituximab. Current trials are testing RIT as initial therapy with rituximab maintenance, as adjuvant therapy after chemotherapy, or in high-dose protocols with stem-cell support.
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PMID:Radioimmunotherapy for B-cell non-Hodgkin lymphoma. 1699 75


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