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Mark S Kaminski - One of the best experts on this subject based on the ideXlab platform.
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iodine I131 Tositumomab
2016Co-Authors: John M. Bennett, Oliver W Press, Andrew D Zelenetz, John P Leonard, Mark S Kaminski, Julie M. Vose, Susan J. Knox, Ra Horning, John A. Radford, Stewart M. KrollAbstract:of treatment-related myelodysplastic syndromes and acute myeloid leukemia in patients with non-Hodgkin lymphoma treated with Tositumomab an
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Observational Retrospective Study of Altered Biodistribution of Tositumomab and 131I-Tositumomab
Journal of Nuclear Medicine, 2015Co-Authors: Richard L. Wahl, Thierry Horner, Thomas S. Lin, Mark S KaminskiAbstract:UNLABELLED The Tositumomab/(131)I-Tositumomab radioimmunotherapy regimen is administered as a dosimetric dose followed by a therapeutic dose. The biodistribution of the dosimetric dose is assessed by quantitative calculations of whole-body residence time (TBRT) and visual examination of whole-body γ-camera images, to determine the administered radioactivity dose and whether a therapeutic dose can be administered. We investigated whether altered biodistribution of (131)I-Tositumomab could be identified using quantitative TBRT. METHODS BioClinica, Inc., provided γ-camera images to an independent reviewer to assess altered (131)I-Tositumomab biodistribution in patients reported to a registry. RESULTS Of 2,649 therapeutic doses, 5 (0.2%) were cancelled because of altered biodistribution as determined by γ-camera images and TBRT. Of these, 3 γ-camera images were assessed by the independent reviewer; one showed altered biodistribution (0.04%) and was in agreement with the TBRT on-site calculation. CONCLUSION TBRT alone should be used to determine altered biodistribution and hence whether to administer the therapeutic dose.
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Phase II study of low-dose methotrexate to reduce the incidence of human anti-mouse antibodies in patients receiving I-131 Tositumomab as first-line treatment for follicular lymphoma.
Journal of Clinical Oncology, 2013Co-Authors: Daniel Lebovic, Judith Estes, Yuni K. Dewaraja, Anca M. Avram, Kathryn Jacobi, Sara Goeman, Sarah Kyle, Erica Chapman, Kent A. Griffith, Mark S KaminskiAbstract:e19519 Background: I-131 Tositumomab is a radiolabeled murine anti-CD20 antibody. In a frontline phase II follicular lymphoma (FL) trial, treatment with I-131 Tositumomab produced a 95% ORR with 75% CR (NEJM 352:441, 2005). Median PFS was 6.1 yrs. However, 30% of patients (pts) developed high levels of human anti-mouse antibodies (HAMA) and a serum sickness syndrome within 7 weeks of treatment (early onset HAMA). The 5-yr PFS for this group was 35% compared to 70% for the others (p = 0.003). Low-dose oral methotrexate (mtx) reduces the incidence of human anti-chimeric antibody (HACA) formation in rheumatoid arthritis pts receiving infliximab. We hypothesized that low-dose mtx would likewise reduce the incidence of early onset HAMA when given in combination with I-131 Tositumomab. Methods: This is a single arm, phase II study in pts with FL, grade 1-2, stage III or IV disease without limits on marrow involvement, and ≥ 1 of the GELF criteria. Prior therapy, other than focal radiotherapy, is not allowed. Pt...
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phase iii randomized intergroup trial of chop plus rituximab compared with chop chemotherapy plus 131iodine Tositumomab for previously untreated follicular non hodgkin lymphoma swog s0016
Journal of Clinical Oncology, 2013Co-Authors: Oliver W Press, Mark S Kaminski, Jonathan W. Friedberg, Joseph M Unger, Michael Leblanc, Lisa M. Rimsza, Myron S Czuczman, Rita M BrazielAbstract:Purpose Advanced follicular lymphomas (FL) are considered incurable with conventional chemotherapy and there is no consensus on the best treatment approach. Southwest Oncology Group (SWOG) and Cancer and Leukemia Group B compared the safety and efficacy of two immunochemotherapy regimens for FL in a phase III randomized intergroup protocol (SWOG S0016) that enrolled 554 patients with previously untreated, advanced-stage FL between March 1, 2001, and September 15, 2008. Patients and Methods Patients were eligible for the study if they had advanced-stage (bulky stage II, III, or IV) evaluable FL of any grade (1, 2, or 3) and had not received previous therapy. In one arm of the study, patients received six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy at 3-week intervals with six doses of rituximab (CHOP-R). In another arm of the study, patients received six cycles of CHOP followed by consolidation with Tositumomab/iodine I-131 Tositumomab radioimmunotherapy (RIT). ...
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A Phase II Study of Consolidation Treatment with Iodione-131 Tositumomab (Bexxar™) in Multiple Myeloma (MM)
Blood, 2012Co-Authors: Daniel Lebovic, Mark S Kaminski, Kent A. Griffith, Tara B. Anderson, Kristen Detweiler-short, Terri L. Jobkar, Malathi Kandarpa, Andrzej JakubowiakAbstract:Abstract 1854 Background: Despite the introduction of novel agents and therapies, MM remains incurable. Approximately 15–20% of MM patients have detectable CD20 expression on their malignant cells. Additionally, preclinical studies evaluating the properties of clonogenic MM cells (“MM stem cells”) suggest that these cells express CD20. However, studies with rituximab, an anti-CD20 antibody have not clearly established CD20 as a valid target in MM. I-131 Tositumomab is a radiolabeled murine anti-CD20 antibody which is highly effective in the treatment of low-grade B-cell NHL and has a well-characterized toxicity profile. In this study, we evaluated the safety and efficacy of consolidation treatment with I-131 Tositumomab in patients with MM who had received ≥1 line of prior treatment. Methods: This was a single arm, phase II, single-center study. All patients had symptomatic MM and had received 1–3 prior treatment regimens. Patients were required to have a stable response to prior therapy of > PR but Results: Between July 2006 and April 2012, sixteen patients were enrolled. Median age was 56 (45–77). Nine were male. The median number of prior treatments was 2. Six patients had CD20 positive MM. In the total population, results were as follows: PD=7, SD=4, MR=1, PR=2, CR=2, for an ORR of 31% (95% CI: 11%-59%). Of the 4 patients with SD, 3 had their data censored at 3 months because they proceeded to transplant, and the other patient has only 3 months of follow up to date. In the CD20 negative population, response rates were PD=6, SD=3, PR=1 for an ORR of 10% (95% CI: Conclusion: I-131 Tositumomab is well-tolerated in patients with previously treated MM and produces objective responses including CRs. ORR was significantly higher in CD20 positive compared with CD20 negative disease: 67% vs. 10% (p=0.036). Achievement of response is delayed compared to what is observed with standard MM therapy. While we continue to investigate its effects on MM “stem cells,” these results indicate that I-131 Tositumomab produces highly durable responses in CD20 positive MM. Disclosures: Off Label Use: Bexxar (I-131 Tositumomab) a radiolabled anti-CD20 antibody. It is approved by the FDA for the treatment of patients with CD20-positive relapsed or refractory, low-grade, follicular, or transformed non-Hodgkin9s lymphoma, including patients with Rituximab-refractory non-Hodgkin9s lymphoma. In this study, Bexxar is used in the treatment of previously treated multiple myeloma. Kaminski:GlaxoSmithKline: Bexxar, Bexxar Patents & Royalties.
Richard L. Wahl - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of Next-Generation Anti-CD20 Antibodies Labeled with 89Zr in Human Lymphoma Xenografts
The Journal of Nuclear Medicine, 2018Co-Authors: Jason T. Yoon, Mark S. Longtine, Bernadette V. Marquez-nostra, Richard L. WahlAbstract:Radioimmunotherapies with monoclonal antibodies to the B-lymphocyte antigen 20 (CD20) are effective treatments for B-cell lymphomas, but U.S. Food and Drug Administration–approved radioimmunotherapies exclusively use radiolabeled murine antibodies, potentially limiting redosing. The Food and Drug Administration recently approved 2 unlabeled anti-CD20 monoclonal antibodies, obinutuzumab and ofatumumab, termed next generation as they are humanized (obinutuzumab) or fully human (ofatumumab), thus potentially allowing a greater potential for redosing than with previous-generation anti-CD20 antibodies, including rituximab (chimeric) and Tositumomab (murine), which contain more murine peptide sequences. We prepared 89Zr-ofatumumab and 89Zr-obinituzumab and assessed their tumor targeting by PET/CT imaging and their biodistribution in a preclinical mouse model with CD20 xenografts to determine whether these antibodies have potential as theranostics or for radioimmunotherapy. Methods: Obinutuzumab, ofatumumab, rituximab, Tositumomab, and human IgG (as control) were radiolabeled with 89Zr. Raji Burkitt lymphoma xenografts were established in severe combined immunodeficient mice. Mice with palpable tumors (n = 4–9) were injected with 89Zr-obinutuzumab, 89Zr-ofatumumab, 89Zr-rituximab, 89Zr-Tositumomab, or 89Zr-IgG, with small-animal PET/CT images acquired at 1, 3, and 7 d after injection, and then sacrificed for biodistribution analyses. Results: At 1, 3, and 7 d after injection, all anti-CD20 antibodies showed clear tumor uptake on PET/CT, with minimal tumor uptake of IgG. Biodistribution data showed significantly (P < 0.005) higher tumor uptake for obinutuzumab (41.4 ± 7.6 percentage injected dose [%ID]/g), ofatumumab (32.6 ± 17.5 %ID/g), rituximab (28.6 ± 7.6 %ID/g), and Tositumomab (28.0 ± 6.5 %ID/g) than IgG (7.2 ± 1.2 %ID/g). Tositumomab had much higher splenic uptake (186.4 ± 49.7 %ID/g, P < 0.001) than the other antibodies. Conclusion: 89Zr-labeled obinutuzumab and ofatumumab localized to tumor as well as or better than labeled rituximab and Tositumomab, 2 monoclonal antibodies that have been used previously in B-cell lymphoma radioimmunotherapy, and both obinutuzumab and ofatumumab have the potential for repeated dosing.
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initial experience with Tositumomab and i 131 labeled Tositumomab for treatment of relapsed refractory hodgkin lymphoma
Molecular Imaging and Biology, 2017Co-Authors: Heather A. Jacene, Yvette L. Kasamon, Richard F. Ambinder, Wayne Kasecamp, Donna Serena, John Crandall, Steven Piantadosi, Richard L. WahlAbstract:Purpose To determine the maximum tolerated dose (MTD) of [131I]Tositumomab in patients with refractory/recurrent Hodgkin lymphoma (HL) and to preliminarily determine if [131I]Tositumomab has activity against HL and if positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]DG) performed 6 weeks post-therapy predicted 12-week response.
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Initial Experience with Tositumomab and I-131-Labeled Tositumomab for Treatment of Relapsed/Refractory Hodgkin Lymphoma
Molecular imaging and biology, 2016Co-Authors: Heather A. Jacene, Yvette L. Kasamon, Richard F. Ambinder, Wayne Kasecamp, Donna Serena, John Crandall, Steven Piantadosi, Richard L. WahlAbstract:Purpose To determine the maximum tolerated dose (MTD) of [131I]Tositumomab in patients with refractory/recurrent Hodgkin lymphoma (HL) and to preliminarily determine if [131I]Tositumomab has activity against HL and if positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]DG) performed 6 weeks post-therapy predicted 12-week response.
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Observational Retrospective Study of Altered Biodistribution of Tositumomab and 131I-Tositumomab
Journal of Nuclear Medicine, 2015Co-Authors: Richard L. Wahl, Thierry Horner, Thomas S. Lin, Mark S KaminskiAbstract:UNLABELLED The Tositumomab/(131)I-Tositumomab radioimmunotherapy regimen is administered as a dosimetric dose followed by a therapeutic dose. The biodistribution of the dosimetric dose is assessed by quantitative calculations of whole-body residence time (TBRT) and visual examination of whole-body γ-camera images, to determine the administered radioactivity dose and whether a therapeutic dose can be administered. We investigated whether altered biodistribution of (131)I-Tositumomab could be identified using quantitative TBRT. METHODS BioClinica, Inc., provided γ-camera images to an independent reviewer to assess altered (131)I-Tositumomab biodistribution in patients reported to a registry. RESULTS Of 2,649 therapeutic doses, 5 (0.2%) were cancelled because of altered biodistribution as determined by γ-camera images and TBRT. Of these, 3 γ-camera images were assessed by the independent reviewer; one showed altered biodistribution (0.04%) and was in agreement with the TBRT on-site calculation. CONCLUSION TBRT alone should be used to determine altered biodistribution and hence whether to administer the therapeutic dose.
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non hodgkin lymphoma radioimmunotherapy using iodine 131 labeled murine anti cd20 antibodies 131i Tositumomab and Tositumomab bexxar
2014Co-Authors: Heather A. Jacene, Richard L. WahlAbstract:The rationale for the use of radioimmunotherapy (RIT) in cancer is that radiolabeled monoclonal antibodies specifically target and irradiate tumor cells while sparing normal tissues. The specific tumor targeting theoretically allows higher doses of radiation to be delivered to tumor as compared to external beam radiation because the effects of the radiation on normal tissues is lesser with RIT. An additional advantage of RIT is that the beta-emissions of the radiolabel target surrounding malignant cells via the cross-fire effect, probably killing those not reached by unlabeled antibody. Tositumomab and Iodine (I 131) Tositumomab (Bexxar® therapeutic regimen) is RIT directed against the CD20 antigen which is effective for the treatment of B-cell non-Hodgkin lymphoma (NHL). This chapter discusses the rationale, development, clinical applications and practical aspects of delivering Tositumomab and Iodine (I 131) Tositumomab (Bexxar® therapeutic regimen).
Oliver W Press - One of the best experts on this subject based on the ideXlab platform.
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iodine I131 Tositumomab
2016Co-Authors: John M. Bennett, Oliver W Press, Andrew D Zelenetz, John P Leonard, Mark S Kaminski, Julie M. Vose, Susan J. Knox, Ra Horning, John A. Radford, Stewart M. KrollAbstract:of treatment-related myelodysplastic syndromes and acute myeloid leukemia in patients with non-Hodgkin lymphoma treated with Tositumomab an
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Radioimmunotherapy consolidation using 131I-Tositumomab for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma in first remission.
Leukemia & lymphoma, 2015Co-Authors: Mazyar Shadman, Oliver W Press, David G Maloney, Ajay K. Gopal, Britt E Kammerer, Pamela S. Becker, Barbara S. Pender, Andrei R. Shustov, John M. PagelAbstract:Despite initial responses to chemoimmunotherapy, relapse and minimal residual disease (MRD) remain major issues in treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients. We administered 131I-Tositumomab to patients in complete response (CR) or partial response (PR) after induction chemotherapy. Toxicities and rate of PR to CR conversion and MRD elimination were assessed three months later. The study stopped prematurely after enrolling 16 patients. Four (25%) were in CR, 12 (75%) in PR, and 12 (75%) had MRD. Three months after treatment with 131I-Tositumomab, CR was achieved (n = 8; 50%) or sustained (n = 4; 25%) in 12 patients and MRD was eliminated in four of 12 patients (33%). Hematologic toxicities were anemia in one patient (6%), neutropenia in 13 (81%), and thrombocytopenia in eight (50%). Two patients (12%) developed MDS 17 and 20 months after consolidation. Consolidation with 131I-Tositumomab for CLL/SLL patients in first remission is feasible and may provide the...
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Myeloablative I-131-Tositumomab with escalating doses of fludarabine and autologous hematopoietic transplantation for adults age ≥ 60 years with B cell lymphoma.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2014Co-Authors: Ajay K. Gopal, David G Maloney, John M. Pagel, Ted Gooley, Joseph G Rajendran, Darrell R. Fisher, Frederick R. Appelbaum, Ryan D. Cassaday, Andrew Shields, Oliver W PressAbstract:Abstract Myeloablative therapy and autologous stem cell transplantation (ASCT) are underutilized in older patients with B cell non-Hodgkin (B-NHL) lymphoma. We hypothesized that myeloablative doses of 131 I-Tositumomab could be augmented by concurrent fludarabine, based on preclinical data indicating synergy. Patients were ≥ 60 years of age and had high-risk, relapsed, or refractory B-NHL. Therapeutic infusions of 131 I-Tositumomab were derived from individualized organ-specific absorbed dose estimates delivering ≤ 27 Gy to critical organs. Fludarabine was initiated 72 hours later followed by ASCT to define the maximally tolerated dose. Thirty-six patients with a median age of 65 years (range, 60 to 76), 2 (range, 1 to 9) prior regimens, and 33% with chemoresistant disease were treated on this trial. Dose-limiting organs included lung (30), kidney (4), and liver (2) with a median administered 131 I activity of 471 mCi (range, 260 to 1620). Fludarabine was safely escalated to 30 mg/m 2 × 7 days. Engraftment was prompt, there were no early treatment-related deaths, and 2 patients had ≥ grade 4 nonhematologic toxicities. The estimated 3-year overall survival, progression-free survival, and nonrelapse mortality were 54%, 53%, and 7%, respectively (median follow up of 3.9 years). Fludarabine up to 210 mg/m 2 can be safely delivered with myeloablative 131 I-Tositumomab and ASCT in older adults with B-NHL.
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131I-Tositumomab Consolidation Radioimmunotherapy (RIT) In Patients With B-Cell Chronic Lymphocytic Leukemia (CLL) Or Small Lymphocytic Lymphoma (SLL) In First Remission
Blood, 2013Co-Authors: Ajay K. Gopal, Oliver W Press, David G Maloney, Britt E Kammerer, Pamela S. Becker, Barbara S. Pender, Andrei R. Shustov, Raya Mawad, John M. PagelAbstract:Background Despite the initial response to combination chemotherapy in CLL/SLL patients, disease relapse and minimal residual disease (MRD) remain major issues in treatment of these diseases. Therefore, developing more effective treatments for CLL/SLL patients is a necessity. One strategy is to eliminate persistent disease using radioimmunotherapy (RIT), such as 131I-Tositumomab (Bexxar®), as consolidation after an objective complete (CR) or partial response (PR) after an induction regimen. In this study we investigated the tolerability and efficacy of standard non-myeloablative doses of 131I-Tositumomab following primary induction chemotherapy in CLL/SLL patients in first remission. Patients and Methods Patients older than 18 with CLL/SLL with indication for treatment were included if they were in first CR or PR from prior treatments and had
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131i Tositumomab consolidation radioimmunotherapy rit in patients with b cell chronic lymphocytic leukemia cll or small lymphocytic lymphoma sll in first remission
Blood, 2013Co-Authors: Ajay K. Gopal, Oliver W Press, David G Maloney, Pamela S. Becker, Barbara S. Pender, Andrei R. Shustov, Raya Mawad, Britt Kammerer, John M. PagelAbstract:Background Despite the initial response to combination chemotherapy in CLL/SLL patients, disease relapse and minimal residual disease (MRD) remain major issues in treatment of these diseases. Therefore, developing more effective treatments for CLL/SLL patients is a necessity. One strategy is to eliminate persistent disease using radioimmunotherapy (RIT), such as 131I-Tositumomab (Bexxar®), as consolidation after an objective complete (CR) or partial response (PR) after an induction regimen. In this study we investigated the tolerability and efficacy of standard non-myeloablative doses of 131I-Tositumomab following primary induction chemotherapy in CLL/SLL patients in first remission. Patients and Methods Patients older than 18 with CLL/SLL with indication for treatment were included if they were in first CR or PR from prior treatments and had <25% bone marrow involvement and acceptable peripheral counts. 131I-Tositumomab (75 cGy total-body dose) was delivered between days 90 and 180 from the first day of the last chemotherapy treatment. The dose was reduced to 65 cGy in cases of thrombocytopenia (between 100,000-150,000/µL). Three months after the treatment dose, efficacy and response criteria were specified per NCI working group guidelines and toxicity assessments were recorded based on the CTCAEv3.0. Rituximab levels were determined using ELISA with a monoclonal anti-rituximab idiotype antibody. Results 16 patients (CLL11, SLL 5) received consolidative 131I-Tositumomab in first remission between 2005-2012. The median age was 61 (38-78). Seven patients (43.7%) had high-risk disease based on cytogenetics or molecular profile. Two patients (12.5%) had 11q deletion and one had mutated TP53 (6.25%). Increased CD38 and ZAP-70 expression was present in 3 of 11 and 6 of 7 patients who were tested and unmutated IgVH was detected in 1 of 3 patients. Twelve patients (75%) were in PR when entered the study while 4 (25%) were in CR. Eight patients (50%) had minimal residual disease (MRD) assessed by multiparametric flow cytometry (MFC). Prior chemotherapy consisted of FR in 9 patients (56.2%), FCR in 4 patients (25%), BR in 2 patients (12.5%) and R-CHOP in 1 patient (6.2%). The median time from the first day of the last treatment cycle to the RIT dose was 15.4 weeks (10 - 29). 7 patients (43.7%) needed dose reduction. At 3 months, CR was achieved or sustained in 12 patients (80%). Conversion from PR to CR following RIT occurred in 4 of 8 patients (50%). Likewise, 131I-Tositumomab eliminated MRD in 4 of 8 patients (50%) by negative MFC at 3 months. One patient (6.6%) had PR, one (6.6%) had nodular PR and one had disease progression (6.6%) after administration of 131I-Tositumomab. Lymphadenopathy was improved in 83% (5 of 6) of the patients with measureable disease prior to 131I-Tositumomab. Overall, the patients with CR at 3 months had significantly higher levels of pre-treatment Rituximab levels (11.0 vs. 2.32 µg/ml, p = 0.01. There was no difference in the pre-treatment levels in patients with pre-treatment MRD who had a negative MFC analysis at 3 months compared to the ones to had residual MRD (12.5 vs. 7.6 µg/ml, p = 0.50) or in patients with PR before receiving 131I-Tositumomab who achieved CR at 3 months compared to the ones who did not (11.7 vs. 5.8 µg/ml, p = 0.19). These Results suggest that the levels of Rituximab may be blocking CD20 sites at the lymph node and/or marrow level. The median follow-up was 9.4 months (2.7-54.3). Hematologic toxicities at 3 months were grade 3 anemia in 1 patient (6.2%), grade 3 or 4 neutropenia in 13 (81%), and grade 3 or 4 thrombocytopenia in 8 (50%). Six patients (37.5%) required blood or platelet transfusions. Two patients (12.5%) needed myeloid growth factor support. One patient was hospitalized within 3 months of RIT for neutropenia-related sepsis/typhlitis. Two patients (12.5%) had disease progression and dysplastic changes were found in one. One patient died 3 years after treatment for an unrelated medical reason. Persistent cytopenias were reported in 4 patients (25%) during the follow-up period. Conclusion Overall, consolidation RIT with 131I-Tositumomab after first remission appears to be a feasible approach and may provide the potential benefit of converting PR to CR or eliminating MRD in CLL/SLL patients. Further long–term follow-up to assess possible prolonged side effects and clinical effectiveness of this approach remain on-going. ![Figure][1] Disclosures: Off Label Use: Bexxar is not FDA approved for consolidation of CLL. Gopal: GSK : Research Funding. Becker: Pfizer: Consultancy. Maloney: GSK: Consultancy. Press: Roche/Genentech: Consultancy. [1]: pending:yes
John P Leonard - One of the best experts on this subject based on the ideXlab platform.
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iodine I131 Tositumomab
2016Co-Authors: John M. Bennett, Oliver W Press, Andrew D Zelenetz, John P Leonard, Mark S Kaminski, Julie M. Vose, Susan J. Knox, Ra Horning, John A. Radford, Stewart M. KrollAbstract:of treatment-related myelodysplastic syndromes and acute myeloid leukemia in patients with non-Hodgkin lymphoma treated with Tositumomab an
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cyclophosphamide vincristine and prednisone followed by Tositumomab and iodine 131 Tositumomab in patients with untreated low grade follicular lymphoma eight year follow up of a multicenter phase ii study
Journal of Clinical Oncology, 2010Co-Authors: Brian K Link, Mark S Kaminski, Morton Coleman, Peter Martin, Stanley J Goldsmith, John P LeonardAbstract:Purpose The efficacy and safety of cyclophosphamide, vincristine, and prednisone (CVP) followed by Tositumomab and iodine-131 (131I) –Tositumomab therapy were evaluated in a multicenter phase II study in patients with untreated low-grade follicular lymphoma. Patients and Methods Patients received six cycles of CVP followed by one cycle of Tositumomab and 131I-Tositumomab (one dosimetric dose and one therapeutic dose). The treatment was evaluated for efficacy and safety. Results All 30 patients enrolled completed CVP as well as Tositumomab and 131I-Tositumomab therapy. The overall response rate after completion of therapy was 100%, with 28 patients (93%) achieving a complete response (CR) and two patients achieving a partial response. Of the 17 patients with bone marrow involvement at enrollment, 15 achieved a confirmed CR. Fourteen of 15 patients with bulky disease (≥ 5 cm) had a CR after treatment completion. After a median follow-up of 8.4 years, the median response duration had not been reached (range,...
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Cyclophosphamide, Vincristine, and Prednisone Followed by Tositumomab and Iodine-131–Tositumomab in Patients With Untreated Low-Grade Follicular Lymphoma: Eight-Year Follow-Up of a Multicenter Phase II Study
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2010Co-Authors: Brian K Link, Mark S Kaminski, Morton Coleman, Peter Martin, Stanley J Goldsmith, John P LeonardAbstract:Purpose The efficacy and safety of cyclophosphamide, vincristine, and prednisone (CVP) followed by Tositumomab and iodine-131 (131I) –Tositumomab therapy were evaluated in a multicenter phase II study in patients with untreated low-grade follicular lymphoma. Patients and Methods Patients received six cycles of CVP followed by one cycle of Tositumomab and 131I-Tositumomab (one dosimetric dose and one therapeutic dose). The treatment was evaluated for efficacy and safety. Results All 30 patients enrolled completed CVP as well as Tositumomab and 131I-Tositumomab therapy. The overall response rate after completion of therapy was 100%, with 28 patients (93%) achieving a complete response (CR) and two patients achieving a partial response. Of the 17 patients with bone marrow involvement at enrollment, 15 achieved a confirmed CR. Fourteen of 15 patients with bulky disease (≥ 5 cm) had a CR after treatment completion. After a median follow-up of 8.4 years, the median response duration had not been reached (range,...
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Radioimmunotherapy with Tositumomab and iodine-131 Tositumomab for non-Hodgkin's lymphoma.
Biologics : targets & therapy, 2007Co-Authors: Biree Andemariam, John P LeonardAbstract:With the success of targeted monoclonal antibody therapy in non-Hodgkin’s lymphoma, attempts were made to further improve efficacy through the addition of a radioisotope. A goal of radioimmunotherapy is to utilize the monoclonal antibody to deliver radiation to a tumor bed with relatively limited toxicity to the surrounding normal tissues. I-131 Tositumomab is an iodine-131 labeled anti-CD20 murine IgG2a monoclonal antibody and is one of two FDA-approved radioimmunotherapeutic drugs for patients with non-Hodgkin’s lymphoma (NHL). For more than a decade now, radiolabeled Tositumomab has principally been evaluated in low-grade and transformed low-grade NHL patients with proven efficacy in both the up-front and salvage settings. Studies have included its use as a single agent, in combination with chemotherapy and as part of a conditioning regimen for autologous stem cell transplantation. These data suggest that this agent has an important role in the treatment of patients with B cell lymphoma.
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Re-treatment with Tositumomab and Iodine I 131 Tositumomab in patients with non-Hodgkin lymphoma who had previously responded to Tositumomab and Iodine I 131 Tositumomab
Journal of Clinical Oncology, 2005Co-Authors: Mark S Kaminski, John P Leonard, S. Kroll, Stephanie A. Gregory, Susan J. Knox, John Radford, Richard L. WahlAbstract:PURPOSE To study efficacy and safety of re-treatment with I-131 Tositumomab in patients with low-grade, follicular, or transformed low-grade B-cell lymphoma who relapsed following a response to I-131 Tositumomab. PATIENTS AND METHODS A prior response >/= 3 months to I-131 Tositumomab was required. The single therapeutic dose following a dosimetric dose was adjusted to give the same total body dose (in Gy) as that used for the original dose, or was attenuated if the platelet count was less than 150,000 per mm(3) or if the prior treatment resulted in grade 4 cytopenias lasting longer than 7 days. Results Of 32 patients enrolled, 28 completed the therapeutic dose. A median of four therapies were given before re-treatment. Eighteen (56%) of 32 patients had a complete or partial response (median duration, 15.2 months); eight (25%) had a complete response (median duration, 35 months). Five continue in response from 1.8 to 5.7 years, with a median follow-up of 35 months. The overall median response duration was not significantly different for the two treatments, with no clinical factors predicting response or its duration. Ten of 18 re-responders had longer responses with re-treatment, with five having responses >/= 1.5 years longer. Grade 3/4 neutropenia and thrombocytopenia occurred in 50% and 43% of patients, respectively, similar to initial treatment. Antimouse antibodies developed in 10% of patients, and 12% developed elevated serum thyroid-stimulating hormone. Six patients were diagnosed with second malignancies, including four patients who developed myelodysplastic syndrome (one who had not received the therapeutic dose) and one with acute myelogenous leukemia. CONCLUSION Re-treatment with I-131 Tositumomab following a previous response can produce second responses that can be durable.
David G Maloney - One of the best experts on this subject based on the ideXlab platform.
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Radioimmunotherapy consolidation using 131I-Tositumomab for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma in first remission.
Leukemia & lymphoma, 2015Co-Authors: Mazyar Shadman, Oliver W Press, David G Maloney, Ajay K. Gopal, Britt E Kammerer, Pamela S. Becker, Barbara S. Pender, Andrei R. Shustov, John M. PagelAbstract:Despite initial responses to chemoimmunotherapy, relapse and minimal residual disease (MRD) remain major issues in treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients. We administered 131I-Tositumomab to patients in complete response (CR) or partial response (PR) after induction chemotherapy. Toxicities and rate of PR to CR conversion and MRD elimination were assessed three months later. The study stopped prematurely after enrolling 16 patients. Four (25%) were in CR, 12 (75%) in PR, and 12 (75%) had MRD. Three months after treatment with 131I-Tositumomab, CR was achieved (n = 8; 50%) or sustained (n = 4; 25%) in 12 patients and MRD was eliminated in four of 12 patients (33%). Hematologic toxicities were anemia in one patient (6%), neutropenia in 13 (81%), and thrombocytopenia in eight (50%). Two patients (12%) developed MDS 17 and 20 months after consolidation. Consolidation with 131I-Tositumomab for CLL/SLL patients in first remission is feasible and may provide the...
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myeloablative i 131 Tositumomab with escalating doses of fludarabine and autologous hematopoietic transplantation for adults age 60 years with b cell lymphoma
Biology of Blood and Marrow Transplantation, 2014Co-Authors: David G Maloney, Ajay K. Gopal, John M. Pagel, Ted Gooley, Joseph G Rajendran, Darrell R. Fisher, Frederick R. AppelbaumAbstract:Abstract Myeloablative therapy and autologous stem cell transplantation (ASCT) are underutilized in older patients with B cell non-Hodgkin (B-NHL) lymphoma. We hypothesized that myeloablative doses of 131 I-Tositumomab could be augmented by concurrent fludarabine, based on preclinical data indicating synergy. Patients were ≥ 60 years of age and had high-risk, relapsed, or refractory B-NHL. Therapeutic infusions of 131 I-Tositumomab were derived from individualized organ-specific absorbed dose estimates delivering ≤ 27 Gy to critical organs. Fludarabine was initiated 72 hours later followed by ASCT to define the maximally tolerated dose. Thirty-six patients with a median age of 65 years (range, 60 to 76), 2 (range, 1 to 9) prior regimens, and 33% with chemoresistant disease were treated on this trial. Dose-limiting organs included lung (30), kidney (4), and liver (2) with a median administered 131 I activity of 471 mCi (range, 260 to 1620). Fludarabine was safely escalated to 30 mg/m 2 × 7 days. Engraftment was prompt, there were no early treatment-related deaths, and 2 patients had ≥ grade 4 nonhematologic toxicities. The estimated 3-year overall survival, progression-free survival, and nonrelapse mortality were 54%, 53%, and 7%, respectively (median follow up of 3.9 years). Fludarabine up to 210 mg/m 2 can be safely delivered with myeloablative 131 I-Tositumomab and ASCT in older adults with B-NHL.
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Myeloablative I-131-Tositumomab with escalating doses of fludarabine and autologous hematopoietic transplantation for adults age ≥ 60 years with B cell lymphoma.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2014Co-Authors: Ajay K. Gopal, David G Maloney, John M. Pagel, Ted Gooley, Joseph G Rajendran, Darrell R. Fisher, Frederick R. Appelbaum, Ryan D. Cassaday, Andrew Shields, Oliver W PressAbstract:Abstract Myeloablative therapy and autologous stem cell transplantation (ASCT) are underutilized in older patients with B cell non-Hodgkin (B-NHL) lymphoma. We hypothesized that myeloablative doses of 131 I-Tositumomab could be augmented by concurrent fludarabine, based on preclinical data indicating synergy. Patients were ≥ 60 years of age and had high-risk, relapsed, or refractory B-NHL. Therapeutic infusions of 131 I-Tositumomab were derived from individualized organ-specific absorbed dose estimates delivering ≤ 27 Gy to critical organs. Fludarabine was initiated 72 hours later followed by ASCT to define the maximally tolerated dose. Thirty-six patients with a median age of 65 years (range, 60 to 76), 2 (range, 1 to 9) prior regimens, and 33% with chemoresistant disease were treated on this trial. Dose-limiting organs included lung (30), kidney (4), and liver (2) with a median administered 131 I activity of 471 mCi (range, 260 to 1620). Fludarabine was safely escalated to 30 mg/m 2 × 7 days. Engraftment was prompt, there were no early treatment-related deaths, and 2 patients had ≥ grade 4 nonhematologic toxicities. The estimated 3-year overall survival, progression-free survival, and nonrelapse mortality were 54%, 53%, and 7%, respectively (median follow up of 3.9 years). Fludarabine up to 210 mg/m 2 can be safely delivered with myeloablative 131 I-Tositumomab and ASCT in older adults with B-NHL.
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131i Tositumomab consolidation radioimmunotherapy rit in patients with b cell chronic lymphocytic leukemia cll or small lymphocytic lymphoma sll in first remission
Blood, 2013Co-Authors: Ajay K. Gopal, Oliver W Press, David G Maloney, Pamela S. Becker, Barbara S. Pender, Andrei R. Shustov, Raya Mawad, Britt Kammerer, John M. PagelAbstract:Background Despite the initial response to combination chemotherapy in CLL/SLL patients, disease relapse and minimal residual disease (MRD) remain major issues in treatment of these diseases. Therefore, developing more effective treatments for CLL/SLL patients is a necessity. One strategy is to eliminate persistent disease using radioimmunotherapy (RIT), such as 131I-Tositumomab (Bexxar®), as consolidation after an objective complete (CR) or partial response (PR) after an induction regimen. In this study we investigated the tolerability and efficacy of standard non-myeloablative doses of 131I-Tositumomab following primary induction chemotherapy in CLL/SLL patients in first remission. Patients and Methods Patients older than 18 with CLL/SLL with indication for treatment were included if they were in first CR or PR from prior treatments and had <25% bone marrow involvement and acceptable peripheral counts. 131I-Tositumomab (75 cGy total-body dose) was delivered between days 90 and 180 from the first day of the last chemotherapy treatment. The dose was reduced to 65 cGy in cases of thrombocytopenia (between 100,000-150,000/µL). Three months after the treatment dose, efficacy and response criteria were specified per NCI working group guidelines and toxicity assessments were recorded based on the CTCAEv3.0. Rituximab levels were determined using ELISA with a monoclonal anti-rituximab idiotype antibody. Results 16 patients (CLL11, SLL 5) received consolidative 131I-Tositumomab in first remission between 2005-2012. The median age was 61 (38-78). Seven patients (43.7%) had high-risk disease based on cytogenetics or molecular profile. Two patients (12.5%) had 11q deletion and one had mutated TP53 (6.25%). Increased CD38 and ZAP-70 expression was present in 3 of 11 and 6 of 7 patients who were tested and unmutated IgVH was detected in 1 of 3 patients. Twelve patients (75%) were in PR when entered the study while 4 (25%) were in CR. Eight patients (50%) had minimal residual disease (MRD) assessed by multiparametric flow cytometry (MFC). Prior chemotherapy consisted of FR in 9 patients (56.2%), FCR in 4 patients (25%), BR in 2 patients (12.5%) and R-CHOP in 1 patient (6.2%). The median time from the first day of the last treatment cycle to the RIT dose was 15.4 weeks (10 - 29). 7 patients (43.7%) needed dose reduction. At 3 months, CR was achieved or sustained in 12 patients (80%). Conversion from PR to CR following RIT occurred in 4 of 8 patients (50%). Likewise, 131I-Tositumomab eliminated MRD in 4 of 8 patients (50%) by negative MFC at 3 months. One patient (6.6%) had PR, one (6.6%) had nodular PR and one had disease progression (6.6%) after administration of 131I-Tositumomab. Lymphadenopathy was improved in 83% (5 of 6) of the patients with measureable disease prior to 131I-Tositumomab. Overall, the patients with CR at 3 months had significantly higher levels of pre-treatment Rituximab levels (11.0 vs. 2.32 µg/ml, p = 0.01. There was no difference in the pre-treatment levels in patients with pre-treatment MRD who had a negative MFC analysis at 3 months compared to the ones to had residual MRD (12.5 vs. 7.6 µg/ml, p = 0.50) or in patients with PR before receiving 131I-Tositumomab who achieved CR at 3 months compared to the ones who did not (11.7 vs. 5.8 µg/ml, p = 0.19). These Results suggest that the levels of Rituximab may be blocking CD20 sites at the lymph node and/or marrow level. The median follow-up was 9.4 months (2.7-54.3). Hematologic toxicities at 3 months were grade 3 anemia in 1 patient (6.2%), grade 3 or 4 neutropenia in 13 (81%), and grade 3 or 4 thrombocytopenia in 8 (50%). Six patients (37.5%) required blood or platelet transfusions. Two patients (12.5%) needed myeloid growth factor support. One patient was hospitalized within 3 months of RIT for neutropenia-related sepsis/typhlitis. Two patients (12.5%) had disease progression and dysplastic changes were found in one. One patient died 3 years after treatment for an unrelated medical reason. Persistent cytopenias were reported in 4 patients (25%) during the follow-up period. Conclusion Overall, consolidation RIT with 131I-Tositumomab after first remission appears to be a feasible approach and may provide the potential benefit of converting PR to CR or eliminating MRD in CLL/SLL patients. Further long–term follow-up to assess possible prolonged side effects and clinical effectiveness of this approach remain on-going. ![Figure][1] Disclosures: Off Label Use: Bexxar is not FDA approved for consolidation of CLL. Gopal: GSK : Research Funding. Becker: Pfizer: Consultancy. Maloney: GSK: Consultancy. Press: Roche/Genentech: Consultancy. [1]: pending:yes
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131I-Tositumomab Consolidation Radioimmunotherapy (RIT) In Patients With B-Cell Chronic Lymphocytic Leukemia (CLL) Or Small Lymphocytic Lymphoma (SLL) In First Remission
Blood, 2013Co-Authors: Ajay K. Gopal, Oliver W Press, David G Maloney, Britt E Kammerer, Pamela S. Becker, Barbara S. Pender, Andrei R. Shustov, Raya Mawad, John M. PagelAbstract:Background Despite the initial response to combination chemotherapy in CLL/SLL patients, disease relapse and minimal residual disease (MRD) remain major issues in treatment of these diseases. Therefore, developing more effective treatments for CLL/SLL patients is a necessity. One strategy is to eliminate persistent disease using radioimmunotherapy (RIT), such as 131I-Tositumomab (Bexxar®), as consolidation after an objective complete (CR) or partial response (PR) after an induction regimen. In this study we investigated the tolerability and efficacy of standard non-myeloablative doses of 131I-Tositumomab following primary induction chemotherapy in CLL/SLL patients in first remission. Patients and Methods Patients older than 18 with CLL/SLL with indication for treatment were included if they were in first CR or PR from prior treatments and had
