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Cancer Control : Journal of the Moffitt... Jul 2012Radioimmunotherapy (RIT) is a safe and effective therapeutic option for patients with indolent B-cell non-Hodgkin lymphomas (NHL), in both up-front and... (Review)
Review
BACKGROUND
Radioimmunotherapy (RIT) is a safe and effective therapeutic option for patients with indolent B-cell non-Hodgkin lymphomas (NHL), in both up-front and relapsed/refractory settings. Two approved agents (90Y-ibritumomab tiuxetan and 131I-tositumomab) are available in the United States. Both target CD20 with similar clinical outcomes but with unique clinical considerations and radiation precautions due to the use of varying radioisotopes.
METHODS
This paper reviews the available evidence for these approved RIT agents and examines the recently published and ongoing clinical trials of potential novel indications for aggressive B-cell NHL.
RESULTS
A pretreatment biodistribution evaluation required before administering the 90Y-ibritumomab tiuxetan therapeutic dose has been removed, which once limited its usage. The potential clinical applications of RIT include relapsed/refractory indolent B-cell NHL, diffuse large B-cell lymphoma, indolent lymphoma in the front-line setting, and mantle cell lymphoma. Multiple novel RIT agents are in preclinical and clinical development, and the addition of radiosensitizers or external-beam radiotherapy may act in synergy with RIT for both indolent and aggressive lymphomas. The risk of treatment-related myelodysplastic syndrome does not appear to be higher in patients treated with RIT over those receiving chemotherapy alone.
CONCLUSIONS
RIT is a safe, effective, and significantly underutilized therapy for patients with B-cell NHL, and many studies have demonstrated the efficacy of 90Y-ibritumomab tiuxetan and 131I-tositumomab for relapsed/refractory indolent B-cell lymphomas. Continued research to establish its efficacy for other lymphoma subtypes is warranted.
Topics: Antibodies, Monoclonal; Humans; Iodine Radioisotopes; Lymphoma, B-Cell; Radioimmunotherapy; Radiopharmaceuticals; Yttrium Radioisotopes
PubMed: 22710895
DOI: 10.1177/107327481201900304 -
Cancers Jan 2022Malignant lymphomas represent the most common type of hematologic malignancies. The first clinically approved TDD modalities in lymphoma patients were anti-CD20... (Review)
Review
Malignant lymphomas represent the most common type of hematologic malignancies. The first clinically approved TDD modalities in lymphoma patients were anti-CD20 radioimmunoconjugates (RIT) I-tositumomab and Y-ibritumomab-tiuxetan. The later clinical success of the first approved antibody-drug conjugate (ADC) for the treatment of lymphomas, anti-CD30 brentuximab vedotin, paved the path for the preclinical development and clinical testing of several other ADCs, including polatuzumab vedotin and loncastuximab tesirine. Other modalities of TDD are based on new formulations of "old" cytostatic agents and their passive trapping in the lymphoma tissue by means of the enhanced permeability and retention (EPR) effect. Currently, the diagnostic and restaging procedures in aggressive lymphomas are based on nuclear imaging, namely PET. A theranostic approach that combines diagnostic or restaging lymphoma imaging with targeted treatment represents an appealing innovative strategy in personalized medicine. The future of theranostics will require not only the capability to provide suitable disease-specific molecular probes but also expertise on big data processing and evaluation. Here, we review the concept of targeted drug delivery in malignant lymphomas from RIT and ADC to a wide array of passively and actively targeted nano-sized investigational agents. We also discuss the future of molecular imaging with special focus on monoclonal antibody-based and monoclonal antibody-derived theranostic strategies.
PubMed: 35158894
DOI: 10.3390/cancers14030626 -
The Quarterly Journal of Nuclear... Dec 2004Iodine [(131)I] tositumomab, administered in combination with unlabelled tositumomab, is a novel radioimmunotherapeutic regimen that targets the CD20 antigen present on... (Review)
Review
Iodine [(131)I] tositumomab, administered in combination with unlabelled tositumomab, is a novel radioimmunotherapeutic regimen that targets the CD20 antigen present on normal and malignant B-cells. The efficacy and safety of the non-myeloablative regimen has been demonstrated in follicular and transformed follicular lymphoma over the last decade in a series of clinical studies, culminating in FDA approval in June 2003. In patients with relapsed or refractory disease some remissions have proven to be durable, and frequently longer in duration than previously administered chemotherapeutic agents. As initial therapy for advanced stage follicular lymphoma, response rates are particularly impressive. Toxicity has been principally haematological, with a single nadir at 4-6 weeks post-therapy. Administration is free of many of the side effects of conventional chemotherapy, although concerns about the long term risk of therapy related myelodysplasia persist. The challenge now comes from deciding the correct place of iodine [(131)I] tositumomab in treatment algorithms for follicular and other ''indolent'' lymphomas. Sequential administration after chemotherapy is being actively investigated, as is its role in myeloablative therapy. Issues of cost-benefit aside, it is a significant development in the therapy of these ''chronic'' malignancies.
Topics: Antibodies, Monoclonal; Clinical Trials as Topic; Humans; Lymphoma, Follicular; Practice Patterns, Physicians'; Radiopharmaceuticals; Treatment Outcome
PubMed: 15640794
DOI: No ID Found -
MAbs 2012Therapeutic monoclonal antibodies (mAbs) are currently being approved for marketing in Europe and the United States, as well as other countries, on a regular basis. As...
Therapeutic monoclonal antibodies (mAbs) are currently being approved for marketing in Europe and the United States, as well as other countries, on a regular basis. As more mAbs become available to physicians and patients, keeping track of the number, types, production cell lines, antigenic targets, and dates and locations of approvals has become challenging. Data are presented here for 34 mAbs that were approved in either Europe or the United States (US) as of March 2012, and nimotuzumab, which is marketed outside Europe and the US. Of the 34 mAbs, 28 (abciximab, rituximab, basiliximab, palivizumab, infliximab, trastuzumab, alemtuzumab, adalimumab, tositumomab-I131, cetuximab, ibrituximab tiuxetan, omalizumab, bevacizumab, natalizumab, ranibizumab, panitumumab, eculizumab, certolizumab pegol, golimumab, canakinumab, catumaxomab, ustekinumab, tocilizumab, ofatumumab, denosumab, belimumab, ipilimumab, brentuximab) are currently marketed in Europe or the US. Data for six therapeutic mAbs (muromonab-CD3, nebacumab, edrecolomab, daclizumab, gemtuzumab ozogamicin, efalizumab) that were approved but have been withdrawn or discontinued from marketing in Europe or the US are also included.
Topics: Animals; Antibodies, Monoclonal; Drug Approval; Europe; Humans; Immunotherapy; Marketing; Product Recalls and Withdrawals; United States
PubMed: 22531442
DOI: 10.4161/mabs.19931 -
Theranostics 2021Radioimmunotherapy (RIT) is FDA-approved for the clinical management of liquid malignancies, however, its use for solid malignancies remains a challenge. The putative... (Review)
Review
Radioimmunotherapy (RIT) is FDA-approved for the clinical management of liquid malignancies, however, its use for solid malignancies remains a challenge. The putative benefit of RIT lies in selective targeting of antigens expressed on the tumor surface using monoclonal antibodies, to systemically deliver cytotoxic radionuclides. The past several decades yielded dramatic improvements in the quality, quantity, recent commercial availability of alpha-, beta- and Auger Electron-emitting therapeutic radiometals. Investigators have created new or improved existing bifunctional chelators. These bifunctional chelators bind radiometals and can be coupled to antigen-specific antibodies. In this review, we discuss approaches to develop radiometal-based RITs, including the selection of radiometals, chelators and antibody platforms (i.e. full-length, F(ab'), Fab, minibodies, diabodies, scFv-Fc and nanobodies). We cite examples of the performance of RIT in the clinic, describe challenges to its implementation, and offer insights to address gaps toward translation.
Topics: Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Antineoplastic Agents, Immunological; Chelating Agents; Click Chemistry; Clinical Trials as Topic; Dose Fractionation, Radiation; Drug Delivery Systems; Forecasting; Humans; Immunoglobulin Fab Fragments; Lymphoma, Non-Hodgkin; Mice; Molecular Targeted Therapy; Neoplasm Proteins; Neoplasms, Experimental; Organ Specificity; Precision Medicine; Radiation Tolerance; Radioimmunotherapy; Radiopharmaceuticals; Receptor Protein-Tyrosine Kinases; Single-Chain Antibodies; Single-Domain Antibodies; Yttrium Radioisotopes
PubMed: 33995659
DOI: 10.7150/thno.57177 -
Pharmacological Research Jan 2023New therapies for relapsed/refractory diffuse large B-cell lymphoma (r/rDLBCL) have emerged in recent years, but there have been no comprehensive quantitative... (Meta-Analysis)
Meta-Analysis Review
New therapies for relapsed/refractory diffuse large B-cell lymphoma (r/rDLBCL) have emerged in recent years, but there have been no comprehensive quantitative comparisons of the efficacy of these therapies. In this study, the efficacy characteristics of 11 types of treatment strategy and 63 treatment regimens were compared by model based meta-analysis. We found that compared with monotherapy, association therapy had significant benefits in terms of overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). However, whereas treatment regimens involving chemotherapy contributed to significant improvements in ORR and PFS, OS was not improved. In terms of treatment strategy, we identified chemotherapy in association with immunotherapy sequential autologous stem cell transplantation (ASCT), the association of two different types of immunotherapies, chemotherapy sequential ASCT, chemotherapy in association with immunotherapy, and chemotherapy in association with two types of immunotherapies as showing better efficacy. With respect to specific treatment regimens, we found that the following had better efficacy: rituximab in association with inotuzumab ozogamicin; rituximab in association with carmustine, etoposide, cytarabine, and melphalan sequential ASCT (R-BEAM+ASCT); lenalidomide in association with rituximab, etoposide, cisplatin, cytarabine, and methylprednisolone; iodine-131 tositumomab in association with BEAM sequential ASCT; and chemotherapy sequential chimeric antigen receptor T-cell immunotherapy, with median OS of 48.2, 34.2, 27.8, 25.8, and 25 months, respectively. Moreover, with respect to association therapy, there was a strong correlation between the 6-month PFS and 2-year OS. The findings of this study provide the necessary quantitative information for clinical practice and clinical trial design for the treatment of r/rDLBCL.
Topics: Humans; Rituximab; Etoposide; Hematopoietic Stem Cell Transplantation; Antineoplastic Combined Chemotherapy Protocols; Transplantation, Autologous; Neoplasm Recurrence, Local; Lymphoma, Large B-Cell, Diffuse; Cytarabine
PubMed: 36470547
DOI: 10.1016/j.phrs.2022.106592 -
Journal of Nuclear Medicine : Official... Nov 2015The tositumomab/(131)I-tositumomab radioimmunotherapy regimen is administered as a dosimetric dose followed by a therapeutic dose. The biodistribution of the dosimetric... (Observational Study)
Observational Study
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.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Dose-Response Relationship, Radiation; Humans; Iodine Radioisotopes; Lung; Lymphoma, Non-Hodgkin; Radionuclide Imaging; Retrospective Studies; Tissue Distribution; Whole Body Imaging
PubMed: 26338897
DOI: 10.2967/jnumed.115.156190 -
Journal of Nuclear Medicine : Official... Mar 2002A methodology was developed determining patient releasability after radioimmunotherapy with tositumomab and (131)I-tositumomab for the treatment of non-Hodgkin's...
UNLABELLED
A methodology was developed determining patient releasability after radioimmunotherapy with tositumomab and (131)I-tositumomab for the treatment of non-Hodgkin's lymphoma.
METHODS
Dosimetry data were obtained and analyzed after 157 administrations of (131)I-tositumomab to 139 patients with relapsed or refractory non-Hodgkin's lymphoma. Tositumomab and (131)I-tositumomab therapy included dosimetric (low activity) and therapeutic (high activity) administrations. For each patient, the total-body residence time was calculated after the dosimetric administration from total-body counts obtained over 6 or 7 d and was then used to determine the appropriate therapeutic activity to deliver a specific total-body radiation dose. Patient dose rates at 1 m were measured immediately after the therapeutic infusion. Patient-specific calculations based on the measured total-body residence time and dose rate for (131)I-tositumomab were derived to determine the patient's maximum releasable dose rate at 1 m, estimated radiation dose to maximally exposed individuals, and the amount of time necessary to avoid close contact with others.
RESULTS
The mean administered activity (+/-SD), determined by dosimetry studies for each patient before therapy, was 3,108 +/- 1,073 MBq (84 +/- 29 mCi) (range, 1,221 +/- 5,957 MBq [33--161 mCi]). Immediately after treatment, the mean measured dose rate (+/- SD) at 1 m was 0.109 +/- 0.032 mSv/h (10.9 +/- 3.2 mrem/h; range, 0.04--0.24 mSv/h [4--24 mrem/h]). The measured dose rates were 60% (range, 37%--90%; P < 0.0001) of the theoretic dose rates from a point source in air predicted using the dose equivalent rate per unit activity of (131)I (5.95 x 10(-5) mSv/MBq h [0.22 mrem/mCi h] at 1 m). The mean estimated radiation dose to the maximally exposed individual was 3.06 mSv (306 mrem) (range, 1.95--4.96 mSv [195--496 mrem]). On the basis of current regulatory patient-release criteria, all (131)I-tositumomab--treated patients were determined to be releasable by comparing the dose rate at 1 m with a predetermined maximum releasable dose rate. Detailed instructions were provided to limit family members' exposure.
CONCLUSION
A methodology has been developed for the release of patients administered radioactive materials based on the new Nuclear Regulatory Commission regulations. This approach uses a patient-specific dose calculation based on the measured total-body residence time and dose rate. This analysis shows the feasibility of outpatient radioimmunotherapy with tositumomab and (131)I-tositumomab.
Topics: Adult; Aged; Aged, 80 and over; Ambulatory Care; Antibodies, Monoclonal; Antigens, CD20; Antineoplastic Agents; Caregivers; Female; Humans; Iodine Radioisotopes; Lymphoma, Non-Hodgkin; Male; Middle Aged; Patient Discharge; Radiation Dosage; Radiation Protection; Radioimmunotherapy; Radiotherapy Dosage; Retrospective Studies; United States
PubMed: 11884495
DOI: No ID Found -
The Quarterly Journal of Nuclear... Dec 2004In recent years, advances in the rational design of radiopharmaceuticals have helped in the introduction of clinically useful therapeutic agents into the clinic. In... (Review)
Review
In recent years, advances in the rational design of radiopharmaceuticals have helped in the introduction of clinically useful therapeutic agents into the clinic. In particular radiolabeled monoclonal antibodies such as (90)Y-ibritumomab and (131)I-tositumomab have shown to be clinically successful. More recently, (177)Lu has emerged as an attractive radionuclide for use in systemic radiotherapy. Like 131I, it has a longer half-live than (90)Y which is more suitable to the pharmacokinetics of monoclonal antibodies, but its chemistry is similar to (90)Y and, when internalized, it is retained by the tumor whereas 131I can be quickly released. Metastatic prostate cancer is an attractive target for radioimmunotherapy since the cornerstone of current therapy is hormonal therapy, which is only palliative. Prostate cancer is also known to metastasize to areas such as the lymph nodes and bone marrow, sites that are readily accessible to circulating monoclonal antibodies. This review will look at recent advances to the treatment of metastatic prostate cancer with radiolabeled antibodies with a specific emphasis on (177)Lu-huJ591, a labeled monoclonal antibody currently under clinical evaluation.
Topics: Antibodies, Monoclonal; Humans; Male; Prostatic Neoplasms; Radioimmunotherapy; Radioisotopes; Radiopharmaceuticals; Treatment Outcome
PubMed: 15640793
DOI: No ID Found