Yttrium 90–Labeled Ibritumomab Tiuxetan Radioimmunotherapy Produces High Response Rates and Durable Remissions in Patients with Previously Treated B-Cell Lymphoma

Gordon, Leo I.; Witzig, Thomas E.; Molina, Arturo; Czuczman, Myron S.; Emmanouilides, Christos; Joyce, Robin; Vo, Katie D.; Theuer, Charles P.; Pohlman, Brad; Bartlett, Nancy L.; Wiseman, Greg; Darif, Mohamed; White, Christine

doi:10.3816/clm.2004.n.015

Cited by 114 publications

(47 citation statements)

References 8 publications

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“…These results are in keeping with the 11 and the proportion of long-term responders among the patients with indolent NHL who achieved a CR/CRu with 90 Y-ibritumomab. 7 In patients who had previously received R-CHOP chemotherapy (group B), 90 Y-ibritumomab was less effective, with an ORR of 19%.…”

Section: Discussionsupporting

confidence: 85%

Efficacy and safety of yttrium-90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation

Morschhauser

Illidge

Huglo

et al. 2007

Blood

179

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A prospective, multicenter, nonrandomized phase 2 trial was conducted to evaluate the efficacy and safety of a single dose of yttrium-90 ( 90 Y) ibritumomab tiuxetan in elderly patients in first relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL) ineligible for stem-cell transplantation. Patients had been previously treated with chemotherapy (group A, n ‫؍‬ 76) or chemotherapy plus rituximab (group B, n ‫؍‬ 28). Patients in group A were further divided into patients in whom induction therapy had failed (stratum AI, n ‫؍‬ 33) and patients who had relapsed after achieving complete response (CR; stratum AII, n ‫؍‬ 43). The overall response rate (ORR) was 52% and 53% in strata AI and AII, respectively, and 19% in group B, with CR/CRu rates of 24%, 39.5%, and 12%, respectively. Median progressionfree survival was 5.9 months and 3.5 months in strata AI and AII, respectively, and 1.6 months in group B. Median overall survival was 21.4, 22.4, and 4.6 months in stratum AI, stratum AII, and group B, respectively. Two patients died from thrombocytopenic cerebral bleeding following administration of therapy. Nonhematologic adverse events were mild to moderate. 90 Y-ibritumomab is active in patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) and its further evaluation in phase 3 studies is ongoing. (Blood. 2007;110:54-58)

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Section: Discussionsupporting

confidence: 85%

Efficacy and safety of yttrium-90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation

Morschhauser

Illidge

Huglo

et al. 2007

Blood

179

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“…Compared with rituximab in a randomized phase III study, 90 Y-ibritumomab tiuxetan was shown to induce 34% of CR/CRu vs 20% for rituximab and a median time to progression (TTP) of 15 versus 10.2 months. In patients who achieved CR/CRu TTP was 24.7 months for RIT and 13.2 months for rituximab alone (Gordon et al, 2004b). Other phase II trials with 90 Y-ibritumomab tiuxetan reported CR/Cru rates between 15 and 51% (Wiseman et al, 2002;Witzig et al, 2002a;Gordon et al, 2004a) the follow-up being frequently shorter compared with the present study or that of Davies (Davies et al, 2004).…”

Section: Toxicitycontrasting

confidence: 53%

“…The results published by Davies et al (2004) and our data suggest that 131 I-tositumomab RIT is at least equivalent to 90 Yibritumomab tiuxetan (Zevalin s ) (Gordon et al, 2004b). Indeed, in the rituximab refractory setting, efficacy may be more favourable for 131 I-tositumomab when reviewing two separate phase II studies of both these agents.…”

Section: Toxicitymentioning

confidence: 55%

Long-term complete responses after 131I-tositumomab therapy for relapsed or refractory indolent non-Hodgkin's lymphoma

et al. 2006

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We present the long-term results of 18 chemotherapy relapsed indolent (N ¼ 12) or transformed (N ¼ 6) NHL patients of a phase II anti-CD20 131 I-tositumomab (Bexxar s ) therapy study. The biphasic therapy included two injections of 450 mg unlabelled antibody combined with 131 I-tositumomab once as dosimetric and once as therapeutic activity delivering 75 or 65 cGy whole-body radiation dose to patients with normal or reduced platelet counts, respectively. Two patients were not treated due to disease progression during dosimetry. The overall response rate was 81% in the 16 patients treated, including 50% CR/CRu and 31% PR. Median progression free survival of the 16 patients was 22.5 months. Median overall survival has not been reached after a median observation of 48 months. Median PFS of complete responders (CR/CRu) has not been reached and will be greater than 51 months. Short-term side effects were mainly haematological and transient. Among the relevant long-term side effects, one patient previously treated with CHOP chemotherapy died from secondary myelodysplasia. Four patients developed HAMA. In conclusion, 131 I-tositumomab RIT demonstrated durable responses especially in those patients who achieved a complete response. Six of eight CR/CRu are ongoing after 46 -70 months.

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“…However, there were no significant differences in the duration of response or time to progression. A significant number of subjects can enjoy durable remissions over several years following this form of treatment (Gordon et al, 2004), and it is clear that the radioactive component of the treatment adds to the efficacy (Davis et al, 2004). Additional studies have moved radioimmunotherapy into first-line treatment with impressive results, and accumulating evidence suggests that subsequent treatments can be administered as necessary in the majority of patients (Ansell et al, 2002;Kaminski et al, 2005;Dosik et al, 2006).…”

mentioning

confidence: 99%

Preclinical and clinical evaluation of epratuzumab (anti-CD22 IgG) in B-cell malignancies

Leonard

Goldenberg

2007

Oncogene

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The vast majority of non-Hodgkin's lymphomas are of B-cell phenotype. Development of unlabeled or radiolabeled therapeutic monoclonal antibodies against the cell surface antigen, CD20, has revolutionized the treatment of these malignancies. It is clear that antibodies targeting other B-cell-specific molecules, such as CD22, also offer potential therapeutic benefit. Epratuzumab is a humanized anti-CD22 monoclonal, which has undergone preclinical and phase I/II clinical evaluation in patients with indolent or aggressive lymphoma. Data suggest that this agent is well tolerated, and can induce tumor regressions. Trials are currently evaluating its safety and activity in combination with rituximab (chimeric anti-CD20) and standard chemotherapy are ongoing. Initial results suggest that these regimens have acceptable toxicity, and that epratuzumab warrants further evaluation as an adjunct to standard lymphoma treatment regimens.

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Yttrium 90–Labeled Ibritumomab Tiuxetan Radioimmunotherapy Produces High Response Rates and Durable Remissions in Patients with Previously Treated B-Cell Lymphoma

Cited by 114 publications

References 8 publications

Efficacy and safety of yttrium-90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation

Efficacy and safety of yttrium-90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation

Long-term complete responses after 131I-tositumomab therapy for relapsed or refractory indolent non-Hodgkin's lymphoma

Preclinical and clinical evaluation of epratuzumab (anti-CD22 IgG) in B-cell malignancies

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