The Experts below are selected from a list of 12858 Experts worldwide ranked by ideXlab platform
Oliver W Press - One of the best experts on this subject based on the ideXlab platform.
-
alpha imaging confirmed efficient targeting of cd45 positive cells after astatine 211 211at Radioimmunotherapy for hematopoietic cell transplantation
The Journal of Nuclear Medicine, 2015Co-Authors: Sofia H L Frost, Donald K. Hamlin, Brian W Miller, Tom Back, Erlinda B Santos, Sue E Knoblaugh, Shani L Frayo, Aimee L Kenoyer, Rainer Storb, Oliver W PressAbstract:Alpha-Radioimmunotherapy targeting CD45 may substitute for total body irradiation in hematopoietic cell transplantation (HCT) preparative regimens for lymphoma. Our goal was to optimize the anti-CD45 monoclonal antibody (MAb; CA12.10C12) protein dose for astatine-211 (211At)-Radioimmunotherapy, extending the analysis to include intra-organ 211At activity distribution and α-imaging-based small-scale dosimetry, along with immunohistochemical staining. Methods Eight normal dogs were injected with either 0.75 (n=5) or 1.00 mg/kg (n=3) of 211At-B10-CA12.10C12 (11.5–27.6 MBq/kg). Two were euthanized and necropsied 19–22 hours post injection (p.i.), and six received autologous HCT three days after 211At-Radioimmunotherapy, following lymph node and bone marrow biopsies at 2–4 and/or 19 hours p.i. Blood was sampled to study toxicity and clearance; CD45 targeting was evaluated by flow cytometry. 211At localization and small-scale dosimetry were assessed using two α-imaging systems: α-camera and iQID.
-
Six of 12 Relapsed or Refractory Indolent Lymphoma Patients Treated 10 Years Ago with 131I-Tositumomab Remain in Complete Remission
Journal of nuclear medicine : official publication Society of Nuclear Medicine, 2011Co-Authors: Franz Buchegger, Oliver W Press, Cristian Antonescu, Claudine Helg, Marek Kosinski, John O. Prior, Angelika Bischof Delaloye, Nicolas KettererAbstract:UNLABELLED The purpose of our study was to update the safety and efficacy results of Radioimmunotherapy in relapsed or resistant indolent or transformed non-Hodgkin lymphoma. METHODS More than 9 y ago, we treated 12 indolent and 4 transformed, relapsed or refractory lymphoma patients with a single administration of nonmyeloablative therapy with tositumomab and (131)I-tositumomab. The 16 patients had a mean of 3.1 (range, 1-6) previous chemotherapy and antibody treatments. RESULTS Six of 12 relapsed indolent lymphoma patients remain disease-free a mean of 9.8 y (range, 8.6-10.7 y) after Radioimmunotherapy. Three of 4 transformed lymphoma patients progressed after Radioimmunotherapy, and 1 patient had a partial response of 10 mo. CONCLUSION Optimal patient benefit might be obtained in indolent lymphoma when administering Radioimmunotherapy up-front in combination with chemotherapy and rituximab treatment. However, these results show that Radioimmunotherapy alone achieved long-lasting remissions in 6 of 12 (50%) indolent lymphoma patients in relapse after 1 or multiple chemotherapies.
-
Pretargeted Radioimmunotherapy for B-Cell Lymphomas
Clinical Cancer Research, 2007Co-Authors: Damian J. Green, Ajay K. Gopal, John M. Pagel, Anastasia Pantelias, Nathan Hedin, Yukang Lin, D. Scott Wilbur, Donald K. Hamlin, Oliver W PressAbstract:Relapsed or treatment refractory B-cell lymphomas are currently incurable with conventional chemotherapy and radiation treatments. High-dose chemoradiotherapy and stem cell transplantation can cure some patients with relapsed or refractory lymphoma, but the majority of such patients die of progressive disease. We have investigated the potential utility of pretargeted Radioimmunotherapy using monoclonal antibody-streptavidin, immunoconjugates, and fusion proteins in combination with N -acetylgalactosamine dendrimeric clearing agent and radiometal-labeled 1,4,7,10-tetraazacyclododecane- N,N ′, N ″, N ‴-tetraacetic acid biotin for treatment of lymphomas using mouse and primate models. We have targeted a variety of cell surface antigens, including CD20, CD22, CD45, and HLA-DR, using conventional and pretargeted Radioimmunotherapy. These studies showed the marked superiority of pretargeted Radioimmunotherapy for each of the antigenic targets in terms of superior biodistributions, more complete tumor regressions, and longer survival. We are optimistic that this novel approach will provide a meaningful prolongation of survival for patients with relapsed or refractory lymphomas.
-
Radioimmunotherapy for treatment of B-cell lymphomas and other hematologic malignancies.
Current opinion in hematology, 2007Co-Authors: Steven I. Park, Oliver W PressAbstract:PURPOSE OF REVIEW Radioimmunotherapy has emerged as one of the most promising treatment options for hematologic malignancies. This review will present the latest information on Radioimmunotherapy for treatment of hematologic malignancies in various clinical settings and assess its long-term safety profile. RECENT FINDINGS Recent data suggest that Radioimmunotherapy with 131I-tositumomab or 90Y-ibritumomab tiuxetan not only induces high response rates but also results in durable remissions in patients with relapsed or refractory indolent non-Hodgkin's lymphomas. Even more notable response rates have been observed when Radioimmunotherapy is used as front-line treatment in patients with indolent non-Hodgkin's lymphomas. The use of Radioimmunotherapy has been evaluated in the treatment of aggressive lymphomas with promising results, but it remains investigational. Standard doses of Radioimmunotherapy given as a conditioning regimen for hematopoietic stem-cell transplant or myeloablative doses of Radioimmunotherapy given in conjunction with stem-cell support have yielded encouraging outcomes with durable remissions and a low incidence of treatment-related mortality. SUMMARY The safety and efficacy of Radioimmunotherapy has been demonstrated for patients with B-cell lymphomas and other hematologic malignancies in various clinical settings. A number of randomized phase III clinical trials are currently underway to further define Radioimmunotherapy's role in the treatment of lymphomas.
-
Comparison of Radiation Dose Estimation for Myeloablative Radioimmunotherapy for Relapsed or Recurrent Mantle Cell Lymphoma Using 131I Tositumomab to That of Other Types of Non-Hodgkin's Lymphoma
Cancer biotherapy & radiopharmaceuticals, 2004Co-Authors: Joseph G Rajendran, Oliver W Press, Ajay K. Gopal, Larry Durack, Darrell R. Fisher, Janet F EaryAbstract:Patients with relapsed or refractory mantle cell lymphoma (MCL) demonstrate poor survival after standard treatment. Myeloablative Radioimmunotherapy (RIT) using 131I tositumomab (anti-CD20) has the...
David M. Goldenberg - One of the best experts on this subject based on the ideXlab platform.
-
Cancer Radioimmunotherapy.
Immunotherapy, 2011Co-Authors: Robert M. Sharkey, David M. GoldenbergAbstract:Targeting of radionuclides with antibodies, or Radioimmunotherapy, has been an active field of research spanning nearly 50 years, evolving with advancing technologies in molecular biology and chemistry, and with many important preclinical and clinical studies illustrating the benefits, but also the challenges, which all forms of targeted therapies face. There are currently two radiolabeled antibodies approved for the treatment of non-Hodgkin lymphoma, but Radioimmunotherapy of solid tumors remains a challenge. Novel antibody constructs, focusing on treatment of localized and minimal disease, and pretargeting are all promising new approaches that are currently under investigation.
-
evaluation of response to fractionated Radioimmunotherapy with 90y epratuzumab in non hodgkin s lymphoma by 18f fluorodeoxyglucose positron emission tomography
Haematologica, 2008Co-Authors: Caroline Bodetmilin, Francoise Kraeberbodere, Loic Campion, Steven Le Gouill, B Dupas, Franck Morschhauser, Thomas Gastinne, Jeanluc Harousseau, William A Wegener, David M. GoldenbergAbstract:Background The study aimed to evaluate FDG-PET imaging for early prediction of response to Radioimmunotherapy in patients with non-Hodgkin’s lymphoma. Design and Methods Twenty-seven patients from a large ongoing, multicenter, phase I/II trial of fractionated Radioimmunotherapy using anti-CD22 90Y-epratuzumab underwent FDG-PET imaging. They also underwent assessment by conventional diagnostic methods that included chemotherapy at baseline and six weeks post-Radioimmunotherapy, and every three months until progression. Responses evaluated from conventional methods were classified using International Workshop Response Criteria as complete response, unconfirmed CR, partial response, stable disease, or progression of disease. FDG-PET images were evaluated visually and were classified as complete response, partial response or progression of disease. The gold standard was histology and follow-up. Results A total of 81 paired imaging studies were obtained post-Radioimmunotherapy (including 3 patients after retreatment) and evaluated as complete response (n=34), partial response (n=24) or progression of disease (n=23) by FDG-PET, and complete response (n=12), unconfirmed complete response (n=31), partial response (n=15), stable disease (n=8) or progression of disease (n=15) by conventional methods. Of the 31 responses evaluated as unconfirmed complete response by conventional methods, 20 (65%) were classified as negative for disease (complete response) by PET while the other 11 (35%) were positive for disease (7 partial response and 4 progression of disease). Among 22 assessable PET images acquired at six weeks post-Radioimmunotherapy, the mean time-to-progression was 15.6 months when PET was negative for disease (complete response), compared with 5.4 months when PET was positive (partial response or progression of disease) (p=0.008). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET six weeks after Radioimmunotherapy were 86%, 63%, 80%, 71% and 77% respectively, compared with 36%, 87%, 83%, 44% and 55% respectively using conventional methods. Conclusions A positive assessment of disease by PET acquired six weeks after Radioimmunotherapy corresponded with a shorter time to progression.
-
Evaluation of response to fractionated Radioimmunotherapy with 90Y-epratuzumab in non-Hodgkin’s lymphoma by 18F-fluorodeoxyglucose positron emission tomography
Haematologica, 2008Co-Authors: Caroline Bodet-milin, Loic Campion, Francoise Kraeber-bodere, B Dupas, Franck Morschhauser, Thomas Gastinne, Jeanluc Harousseau, William A Wegener, Steven Le Gouill, David M. GoldenbergAbstract:Background The study aimed to evaluate FDG-PET imaging for early prediction of response to Radioimmunotherapy in patients with non-Hodgkin’s lymphoma. Design and Methods Twenty-seven patients from a large ongoing, multicenter, phase I/II trial of fractionated Radioimmunotherapy using anti-CD22 90Y-epratuzumab underwent FDG-PET imaging. They also underwent assessment by conventional diagnostic methods that included chemotherapy at baseline and six weeks post-Radioimmunotherapy, and every three months until progression. Responses evaluated from conventional methods were classified using International Workshop Response Criteria as complete response, unconfirmed CR, partial response, stable disease, or progression of disease. FDG-PET images were evaluated visually and were classified as complete response, partial response or progression of disease. The gold standard was histology and follow-up. Results A total of 81 paired imaging studies were obtained post-Radioimmunotherapy (including 3 patients after retreatment) and evaluated as complete response (n=34), partial response (n=24) or progression of disease (n=23) by FDG-PET, and complete response (n=12), unconfirmed complete response (n=31), partial response (n=15), stable disease (n=8) or progression of disease (n=15) by conventional methods. Of the 31 responses evaluated as unconfirmed complete response by conventional methods, 20 (65%) were classified as negative for disease (complete response) by PET while the other 11 (35%) were positive for disease (7 partial response and 4 progression of disease). Among 22 assessable PET images acquired at six weeks post-Radioimmunotherapy, the mean time-to-progression was 15.6 months when PET was negative for disease (complete response), compared with 5.4 months when PET was positive (partial response or progression of disease) (p=0.008). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET six weeks after Radioimmunotherapy were 86%, 63%, 80%, 71% and 77% respectively, compared with 36%, 87%, 83%, 44% and 55% respectively using conventional methods. Conclusions A positive assessment of disease by PET acquired six weeks after Radioimmunotherapy corresponded with a shorter time to progression.
-
Radioimmunotherapy of non-Hodgkin's lymphoma: a critical appraisal.
Expert review of clinical immunology, 2005Co-Authors: Robert M. Sharkey, Jack Burton, David M. GoldenbergAbstract:Radioimmunotherapy is a unique form of radiation therapy that uses antibodies to specifically target radionuclides for systemic cancer treatment. While chemotherapy remains the frontline treatment for non-Hodgkin’s lymphoma, two Radioimmunotherapy agents are approved for use in certain follicular and transformed forms of recurrent non-Hodgkin’s lymphoma as a second- or third-line treatment option. However, there are number of clinical trials underway that will likely lead to a more expanded use of this treatment modality in the future. New agents and approaches for Radioimmunotherapy are also being developed that could offer an even greater potential for this new form of therapy.
-
Experimental Radioimmunotherapy of small peritoneal metastases of colorectal origin
International journal of cancer, 2003Co-Authors: Manuel J. Koppe, Wim J G Oyen, David M. Goldenberg, Annemieke C. Soede, Wikke Pels, Robert P. Bleichrodt, Otto C BoermanAbstract:Radioimmunotherapy using radiolabeled monoclonal antibodies (MoAbs) directed against tumor-associated antigens might be an effective treatment modality for small volume disease. Our aim was to optimize an experimental model of Radioimmunotherapy for small peritoneal metastases of colorectal origin using the anti-CEA MoAb MN-14. In nude mice with intraperitoneal (i.p.) LS174T tumors, a protein dose-escalation study was carried out to determine the maximal dose of radioiodinated MN-14 to be used in Radioimmunotherapy. The biodistribution of radioiodinated MN-14 was determined after intravenous (i.v.) and i.p. administration. Finally, the therapeutic efficacy of escalating activity doses of (131)I-labeled MN-14 (62.5-500 microCi) was assessed and compared to that of unlabeled MN-14 or 500 microCi of (131)I-labeled irrelevant control antibody. At protein doses higher than 25 microg, uptake in tumor was reduced, presumably due to saturation of tumor antigen. During the first 24 hours i.p. administration led to higher tumor uptake and higher tumor:blood ratios than i.v. administration. Median survival of the control groups was 38 days (unlabeled MN-14) and 52 days ((131)I-labeled nonspecific antibody). Median survival of the groups treated with increasing activity doses of (131)I-labeled MN-14 was 42 days (62.5 microCi), 49 days (125 microCi), 63 days (250 microCi) and 101 days (500 microCi), respectively (p < 0.0001 compared to unlabeled MN-14). The present study shows that the anti-CEA-antibody MN-14 preferentially accumulates in i.p. LS174T tumor xenografts after both i.p. and i.v. administration. Intraperitoneal Radioimmunotherapy using (131)I-labeled MN-14 delays significantly the outgrowth of peritoneal LS174T metastases, even at relatively low activity doses.
Henry Jardel - One of the best experts on this subject based on the ideXlab platform.
-
consolidation anti cd22 fractionated Radioimmunotherapy with 90 y epratuzumab tetraxetan following r chop in elderly patients with diffuse large b cell lymphoma a prospective single group phase 2 trial
The Lancet Haematology, 2017Co-Authors: Francoise Kraeberbodere, Amandine Pallardy, Herve Maisonneuve, Isabelle Soubeyran, Etienne Daguindau, Loic Campion, Olivier Tournilhac, Steven Le Gouill, Anne Moreau, Henry JardelAbstract:BACKGROUND: Radioimmunotherapy represents a potential option as consolidation after chemoimmunotherapy in patients with diffuse large B-cell lymphoma who are not candidates for transplantation. We aimed to assess activity and toxicity of fractionated Radioimmunotherapy using anti-CD22 (90)Y-epratuzumab tetraxetan as consolidation after front-line induction chemoimmunotherapy in untreated elderly patients with diffuse large B-cell lymphoma. METHODS: We did a prospective, single-group, phase 2 trial at 28 hospitals in France, with patients recruited from 17 hospitals. Eligible patients were aged 60-80 years with bulky stage 2-3 or stage 3-4 CD20-positive diffuse large B-cell lymphoma, previously untreated, and not eligible for transplantation. Patients received six cycles of R-CHOP (rituximab [375 mg/m(2)], cyclophosphamide [750 mg/m(2)], doxorubicin [50 mg/m(2)], and vincristine [1·4 mg/m(2), up to 2 mg] all on day 1, and prednisone [40 mg/m(2)] daily for 5 days), administered every 14 days. 6-8 weeks after R-CHOP, responders received two doses of 15 mCi/m(2) (555 MBq/m(2)) (90)Y-epratuzumab tetraxetan administered 1 week apart. The primary endpoint was 2 year event-free survival in all registered eligible patients who received at least 1 day of study treatment; the safety analysis was done in the same population. This trial is registered with ClinicalTrials.gov, number NCT00906841. FINDINGS: Between Oct 22, 2008, and Dec 16, 2010, we recruited 75 patients, of whom four (5%) were excluded after central pathology review; hence, 71 (95%) patients were included in the analysis. All patients started induction treatment; 57 (80%) received Radioimmunotherapy. With a median follow-up of 37 months (IQR 30-44), the estimated 2 year event-free survival was 75% (95% CI 63-84). Radioimmunotherapy toxicity consisted of grade 3-4 thrombocytopenia in 48 (84%) of 57 patients and neutropenia in 45 (79%) of 57 patients. One patient developed myelodysplastic syndrome 28 months after receiving Radioimmunotherapy and one patient developed acute myeloid leukaemia 5 months after receiving Radioimmunotherapy. INTERPRETATION: Fractionated Radioimmunotherapy with (90)Y-epratuzumab tetraxetan might be appropriate for response consolidation after induction chemotherapy in older patients with advanced diffuse large B-cell lymphoma, but further comparative studies are needed. FUNDING: Immunomedics, Amgen, Canceropole Grand Ouest, the GOELAMS/LYSA group and the French National Agency for Research (Investissements d'Avenir).
-
Consolidation anti-CD22 fractionated Radioimmunotherapy with 90 Y-epratuzumab tetraxetan following R-CHOP in elderly patients with diffuse large B-cell lymphoma: a prospective, single group, phase 2 trial
The Lancet Haematology, 2017Co-Authors: Francoise Kraeber-bodere, Amandine Pallardy, Herve Maisonneuve, Isabelle Soubeyran, Etienne Daguindau, Loic Campion, Olivier Tournilhac, Steven Le Gouill, Anne Moreau, Henry JardelAbstract:Radioimmunotherapy represents a potential option as consolidation after chemoimmunotherapy in patients with diffuse large B-cell lymphoma who are not candidates for transplantation. We aimed to assess activity and toxicity of fractionated Radioimmunotherapy using anti-CD22 90Y-epratuzumab tetraxetan as consolidation after front-line induction chemoimmunotherapy in untreated elderly patients with diffuse large B-cell lymphoma.
Loic Campion - One of the best experts on this subject based on the ideXlab platform.
-
consolidation anti cd22 fractionated Radioimmunotherapy with 90 y epratuzumab tetraxetan following r chop in elderly patients with diffuse large b cell lymphoma a prospective single group phase 2 trial
The Lancet Haematology, 2017Co-Authors: Francoise Kraeberbodere, Amandine Pallardy, Herve Maisonneuve, Isabelle Soubeyran, Etienne Daguindau, Loic Campion, Olivier Tournilhac, Steven Le Gouill, Anne Moreau, Henry JardelAbstract:BACKGROUND: Radioimmunotherapy represents a potential option as consolidation after chemoimmunotherapy in patients with diffuse large B-cell lymphoma who are not candidates for transplantation. We aimed to assess activity and toxicity of fractionated Radioimmunotherapy using anti-CD22 (90)Y-epratuzumab tetraxetan as consolidation after front-line induction chemoimmunotherapy in untreated elderly patients with diffuse large B-cell lymphoma. METHODS: We did a prospective, single-group, phase 2 trial at 28 hospitals in France, with patients recruited from 17 hospitals. Eligible patients were aged 60-80 years with bulky stage 2-3 or stage 3-4 CD20-positive diffuse large B-cell lymphoma, previously untreated, and not eligible for transplantation. Patients received six cycles of R-CHOP (rituximab [375 mg/m(2)], cyclophosphamide [750 mg/m(2)], doxorubicin [50 mg/m(2)], and vincristine [1·4 mg/m(2), up to 2 mg] all on day 1, and prednisone [40 mg/m(2)] daily for 5 days), administered every 14 days. 6-8 weeks after R-CHOP, responders received two doses of 15 mCi/m(2) (555 MBq/m(2)) (90)Y-epratuzumab tetraxetan administered 1 week apart. The primary endpoint was 2 year event-free survival in all registered eligible patients who received at least 1 day of study treatment; the safety analysis was done in the same population. This trial is registered with ClinicalTrials.gov, number NCT00906841. FINDINGS: Between Oct 22, 2008, and Dec 16, 2010, we recruited 75 patients, of whom four (5%) were excluded after central pathology review; hence, 71 (95%) patients were included in the analysis. All patients started induction treatment; 57 (80%) received Radioimmunotherapy. With a median follow-up of 37 months (IQR 30-44), the estimated 2 year event-free survival was 75% (95% CI 63-84). Radioimmunotherapy toxicity consisted of grade 3-4 thrombocytopenia in 48 (84%) of 57 patients and neutropenia in 45 (79%) of 57 patients. One patient developed myelodysplastic syndrome 28 months after receiving Radioimmunotherapy and one patient developed acute myeloid leukaemia 5 months after receiving Radioimmunotherapy. INTERPRETATION: Fractionated Radioimmunotherapy with (90)Y-epratuzumab tetraxetan might be appropriate for response consolidation after induction chemotherapy in older patients with advanced diffuse large B-cell lymphoma, but further comparative studies are needed. FUNDING: Immunomedics, Amgen, Canceropole Grand Ouest, the GOELAMS/LYSA group and the French National Agency for Research (Investissements d'Avenir).
-
Consolidation anti-CD22 fractionated Radioimmunotherapy with 90 Y-epratuzumab tetraxetan following R-CHOP in elderly patients with diffuse large B-cell lymphoma: a prospective, single group, phase 2 trial
The Lancet Haematology, 2017Co-Authors: Francoise Kraeber-bodere, Amandine Pallardy, Herve Maisonneuve, Isabelle Soubeyran, Etienne Daguindau, Loic Campion, Olivier Tournilhac, Steven Le Gouill, Anne Moreau, Henry JardelAbstract:Radioimmunotherapy represents a potential option as consolidation after chemoimmunotherapy in patients with diffuse large B-cell lymphoma who are not candidates for transplantation. We aimed to assess activity and toxicity of fractionated Radioimmunotherapy using anti-CD22 90Y-epratuzumab tetraxetan as consolidation after front-line induction chemoimmunotherapy in untreated elderly patients with diffuse large B-cell lymphoma.
-
evaluation of response to fractionated Radioimmunotherapy with 90y epratuzumab in non hodgkin s lymphoma by 18f fluorodeoxyglucose positron emission tomography
Haematologica, 2008Co-Authors: Caroline Bodetmilin, Francoise Kraeberbodere, Loic Campion, Steven Le Gouill, B Dupas, Franck Morschhauser, Thomas Gastinne, Jeanluc Harousseau, William A Wegener, David M. GoldenbergAbstract:Background The study aimed to evaluate FDG-PET imaging for early prediction of response to Radioimmunotherapy in patients with non-Hodgkin’s lymphoma. Design and Methods Twenty-seven patients from a large ongoing, multicenter, phase I/II trial of fractionated Radioimmunotherapy using anti-CD22 90Y-epratuzumab underwent FDG-PET imaging. They also underwent assessment by conventional diagnostic methods that included chemotherapy at baseline and six weeks post-Radioimmunotherapy, and every three months until progression. Responses evaluated from conventional methods were classified using International Workshop Response Criteria as complete response, unconfirmed CR, partial response, stable disease, or progression of disease. FDG-PET images were evaluated visually and were classified as complete response, partial response or progression of disease. The gold standard was histology and follow-up. Results A total of 81 paired imaging studies were obtained post-Radioimmunotherapy (including 3 patients after retreatment) and evaluated as complete response (n=34), partial response (n=24) or progression of disease (n=23) by FDG-PET, and complete response (n=12), unconfirmed complete response (n=31), partial response (n=15), stable disease (n=8) or progression of disease (n=15) by conventional methods. Of the 31 responses evaluated as unconfirmed complete response by conventional methods, 20 (65%) were classified as negative for disease (complete response) by PET while the other 11 (35%) were positive for disease (7 partial response and 4 progression of disease). Among 22 assessable PET images acquired at six weeks post-Radioimmunotherapy, the mean time-to-progression was 15.6 months when PET was negative for disease (complete response), compared with 5.4 months when PET was positive (partial response or progression of disease) (p=0.008). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET six weeks after Radioimmunotherapy were 86%, 63%, 80%, 71% and 77% respectively, compared with 36%, 87%, 83%, 44% and 55% respectively using conventional methods. Conclusions A positive assessment of disease by PET acquired six weeks after Radioimmunotherapy corresponded with a shorter time to progression.
-
Evaluation of response to fractionated Radioimmunotherapy with 90Y-epratuzumab in non-Hodgkin’s lymphoma by 18F-fluorodeoxyglucose positron emission tomography
Haematologica, 2008Co-Authors: Caroline Bodet-milin, Loic Campion, Francoise Kraeber-bodere, B Dupas, Franck Morschhauser, Thomas Gastinne, Jeanluc Harousseau, William A Wegener, Steven Le Gouill, David M. GoldenbergAbstract:Background The study aimed to evaluate FDG-PET imaging for early prediction of response to Radioimmunotherapy in patients with non-Hodgkin’s lymphoma. Design and Methods Twenty-seven patients from a large ongoing, multicenter, phase I/II trial of fractionated Radioimmunotherapy using anti-CD22 90Y-epratuzumab underwent FDG-PET imaging. They also underwent assessment by conventional diagnostic methods that included chemotherapy at baseline and six weeks post-Radioimmunotherapy, and every three months until progression. Responses evaluated from conventional methods were classified using International Workshop Response Criteria as complete response, unconfirmed CR, partial response, stable disease, or progression of disease. FDG-PET images were evaluated visually and were classified as complete response, partial response or progression of disease. The gold standard was histology and follow-up. Results A total of 81 paired imaging studies were obtained post-Radioimmunotherapy (including 3 patients after retreatment) and evaluated as complete response (n=34), partial response (n=24) or progression of disease (n=23) by FDG-PET, and complete response (n=12), unconfirmed complete response (n=31), partial response (n=15), stable disease (n=8) or progression of disease (n=15) by conventional methods. Of the 31 responses evaluated as unconfirmed complete response by conventional methods, 20 (65%) were classified as negative for disease (complete response) by PET while the other 11 (35%) were positive for disease (7 partial response and 4 progression of disease). Among 22 assessable PET images acquired at six weeks post-Radioimmunotherapy, the mean time-to-progression was 15.6 months when PET was negative for disease (complete response), compared with 5.4 months when PET was positive (partial response or progression of disease) (p=0.008). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET six weeks after Radioimmunotherapy were 86%, 63%, 80%, 71% and 77% respectively, compared with 36%, 87%, 83%, 44% and 55% respectively using conventional methods. Conclusions A positive assessment of disease by PET acquired six weeks after Radioimmunotherapy corresponded with a shorter time to progression.
Ruby F. Meredith - One of the best experts on this subject based on the ideXlab platform.
-
Ongoing investigations and new uses of Radioimmunotherapy in the treatment of non-Hodgkin's lymphoma.
International journal of radiation oncology biology physics, 2006Co-Authors: Ruby F. MeredithAbstract:Studies in radiation oncology are focusing on the optimal use of systemic targeted radionuclide therapy (STaRT) in the treatment of patients with cancer. The two approved Radioimmunotherapy agents, yttrium-90 ibritumomab tiuxetan and iodine-131 tositumomab, are being studied in a range of lymphoid malignancies, from low-grade to aggressive B-cell non-Hodgkin's lymphomas. Studies of standard- and escalated-dose Radioimmunotherapy with or without stem cell support are reviewed, as are Radioimmunotherapy with other therapeutic modalities in these settings. The results of these trials have important implications for clinical practice, and it is hoped that they will further clarify the optimal timing and dosing of these agents.
-
Ongoing investigations and new uses of Radioimmunotherapy in the treatment of non-Hodgkin’s lymphoma
International Journal of Radiation Oncology*Biology*Physics, 2006Co-Authors: Ruby F. MeredithAbstract:Studies in radiation oncology are focusing on the optimal use of systemic targeted radionuclide therapy (STaRT) in the treatment of patients with cancer. The two approved Radioimmunotherapy agents, yttrium-90 ibritumomab tiuxetan and iodine-131 tositumomab, are being studied in a range of lymphoid malignancies, from low-grade to aggressive B-cell non-Hodgkin's lymphomas. Studies of standard- and escalated-dose Radioimmunotherapy with or without stem cell support are reviewed, as are Radioimmunotherapy with other therapeutic modalities in these settings. The results of these trials have important implications for clinical practice, and it is hoped that they will further clarify the optimal timing and dosing of these agents.
-
Pretargeted Radioimmunotherapy.
International journal of radiation oncology biology physics, 2006Co-Authors: Ruby F. Meredith, Donald J BuchsbaumAbstract:This brief review covers the concept of pretargeted Radioimmunotherapy and summarize the results obtained in preclinical animal models and initial phase I clinical trials. Reagents studied have been a bifunctional antibody prepared by crosslinking Fab' fragments from two antibodies with different specificity, one binding the target antigen expressed on tumors and the other binding a radiolabeled peptide. The alternative system is a conjugate of streptavidin linked to the pretargeting agent and radiolabeled biotin. After reaching optimal tumor targeting of the pretargeting agent, a synthetic mono-biotin poly N-acetyl-galactosamine compound was used to clear unbound targeting agent from the circulation before the injection of radiolabeled biotin. Promising therapeutic responses were obtained in various tumor xenograft models in athymic nude mice. A phase I study of an anti-CD20/streptavidin pretargeting agent and 15 mCi/m(2)(90)Y-biotin produced objective responses with minimal toxicity among lymphoma patients, with an average tumor-to-whole-body radiation dose ratio of 49. Pretargeting Radioimmunotherapy approaches have shown higher tumor-to-whole-body ratios than that usually obtained with one-step Radioimmunotherapy.
-
A Novel Monoclonal Antibody Design for Radioimmunotherapy
Cancer biotherapy & radiopharmaceuticals, 2003Co-Authors: Andres Forero, Sui Shen, Ruby F. Meredith, M. B. Khazaeli, D. Mark Carpenter, Jennifer Thornton, Jeffrey Schlom, Albert F. LobuglioAbstract:The generation of chimeric and complementary-determining region (CDR) grafted monoclonal antibodies (MAb) have reduced the immunogenicity problem in the clinical application of Radioimmunotherapy w...
-
Recent progress in Radioimmunotherapy for cancer.
Oncology (Williston Park N.Y.), 1997Co-Authors: Ruby F. Meredith, Albert F. LobuglioAbstract:Radioimmunotherapy allows for the delivery of systemically targeted radiation to areas of disease while relatively sparing normal tissues. Despite numerous challenges, considerable progress has been made in the application of Radioimmunotherapy to a wide variety of human malignancies. The greatest successes have occurred in the treatment of hematologic malignancies. Radioimmunotherapy, with or without stem-cell transplant support, has produced substantial complete remission rates in chemotherapy-resistant B-cell lymphomas. Nonmyeloablative regimens have shown so much promise that they are now being tested as initial therapy for low-grade B-cell lymphomas. Although solid tumor malignancies have been less responsive to Radioimmunotherapy, encouraging results have been obtained with locoregional routes of administrations, especially when the tumor burden is small. Greater tumor-to-normal tissue ratios are achievable with regional administration. Even with intraperitoneal and intrathecal administration, bone marrow suppression remains the dose-limiting toxicity. Ongoing research into new targeting molecules, improved chelation chemistry, and novel isotope utilization is likely to extend the applications of this strategy to other tumor types. The potential for Radioimmunotherapy will be enhanced if this modality can be optimally adapted for integration with other agents and if the administration method can be tailored to the type and distribution of malignancy.