Ibritumomab tiuxetan radioimmunotherapy for patients with relapsed or refractory non-Hodgkin lymphoma and mild thrombocytopenia: a phase II multicenter trial

Wiseman, Gregory A.; Li, Gordon; Multani, Pratik S.; Witzig, Thomas E.; Spies, Stewart; Bartlett, Nancy L.; Schilder, Russell J.; Murray, James L.; Saleh, Mansoor N.; Allen, Richard M.; Grillo-López, Antonio J; White, Christine

doi:10.1182/blood.v99.12.4336

Cited by 248 publications

(102 citation statements)

References 33 publications

(24 reference statements)

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“…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). Therefore, it is clear that both agents have demonstrated high levels of efficacy in patients with relapsed/refractory disease.…”

Section: Toxicitycontrasting

confidence: 47%

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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Section: Toxicitycontrasting

confidence: 47%

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

et al. 2006

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“…Once bound to their respective target, Mab's induce antitumour activity by one of three principle mechanisms: antibody-dependent cell-mediated cytotoxicity (Clynes et al, 2000), interruption of aberrant cell-signalling proteins (Le et al, 2000) or delivery of a cytotoxic moiety such as a drug, radioisotope or toxin to the tumour (Wiseman et al, 2002). Antibody therapy does, however, have a number of limitations such as poor penetration into tumour, selection of apoptosis-resistant tumour clones and inactivation of Mab by serum proteins (Reilly et al, 1995;Jain, 1999).…”

mentioning

confidence: 99%

Expression of the 5T4 oncofoetal antigen in renal cell carcinoma: a potential target for T-cell-based immunotherapy

et al. 2005

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The 5T4 oncofoetal antigen is a heavily glycosylated cell surface protein found on human placental trophoblast and on diverse types of human cancer but is not expressed at significant levels on adult human tissues in health. It therefore satisfies the criteria for a tumour-associated antigen and is an ideal target for the immunotherapy of cancer. We report here that 5T4 is strongly expressed on the majority of renal cell carcinomas and therefore this population of patients is suitable for trials of 5T4-targeted therapies. In particular, we have shown that T cells from renal cell carcinoma patients can be genetically modified to kill 5T4 expressing renal cancer cell lines by introduction of a chimeric-signalling protein. This protein consists of a single chain antibody fragment capable of binding antigen directly at the cell surface and then activating the T cell by virtue of a CD3z-signalling domain. This is a powerful tool that bypasses a number of mechanisms that allow tumours to escape T-cell killing and can be readily scaled up for clinical use.

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“…1 Conventional treatment options for FL patients include multiagent chemotherapy combined with anti-CD20 monoclonal Abs 2,3 or radioimmunotherapy, 4,5 leading to an improvement of median overall survival (OS) of 12-14 years in the last decade. 6 High-dose salvage regimens, including chemotherapy, rituximab and/or TBI, followed by autologous hematopoietic cell transplantation (HCT) have also clearly improved 5-year PFS and OS.…”

Section: Introductionmentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation as curative therapy for non-transformed follicular lymphomas

Heinzelmann

Bethge²,

Beelen

et al. 2016

Bone Marrow Transplant

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Allogeneic hematopoietic cell transplantation (HCT) offers the chance of cure for patients with non-transformed follicular lymphoma (FL), but is associated with the risk of non-relapse mortality (NRM). The aim of this study was to identify subgroups of FL patients who benefit from HCT. The European Society for Blood and Marrow Transplantation (EBMT) Minimum-Essential-A Data of 146 consecutive patients who received HCT for FL between 1998 and 2008 were extracted from the database of the German Registry 'DRST'. Diagnosis of FL was verified by contact with the reference pathologists. Estimated 1-, 2-and 5-year overall survivals (OS) were 67%, 60% and 53%, respectively. Day 100 NRM was 15%. Thirteen out of 33 patients (40%) with treatment-refractory disease (RD) at the time of transplantation survived long term. Univariate statistical analysis suggested limited chronic GvHD, donor age ⩽ 42 years and TBI-based conditioning in treatment refractory patients to correlate with favorable OS. Independent prognostic factors for OS were treatmentsensitive disease and limited chronic GvHD for the whole cohort, and additionally TBI-based conditioning for the treatment refractory subgroup. In contrast, patient age ⩾ 55 years had no impact on outcome. Thus, HCT for FL is associated with acceptable NRM, and offers a substantial chance of cure for patients with RD or advanced age. Donors ⩽ 42 years should be preferred if available.

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Ibritumomab tiuxetan radioimmunotherapy for patients with relapsed or refractory non-Hodgkin lymphoma and mild thrombocytopenia: a phase II multicenter trial

Cited by 248 publications

References 33 publications

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

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

Expression of the 5T4 oncofoetal antigen in renal cell carcinoma: a potential target for T-cell-based immunotherapy

Allogeneic hematopoietic cell transplantation as curative therapy for non-transformed follicular lymphomas

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