Radioimmunotherapy of relapsed or refractory non-Hodgkin's lymphoma (NHL) with IDEC-Y2B8

Wiseman, G.; Witzig, Thomas E.; White, Christine; Grillo-López, Antonio J; Li, Gordon; Emmanouilides, Christos; Raubitschek, Andrew; Dunn, William L.; Chinn, Paul; Gutheil, John; Janakiraman, Nalini; Schilder, Russell J.

doi:10.1016/s0360-3016(98)80112-0

Cited by 14 publications

(16 citation statements)

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“…Dosimetry performed in the patients confirmed radiation doses to be above the range previously reported in trials of standard dose 90 Y-ibritumomab tiuxetan and similar to previous studies of doseescalated RIT in the context of autologous HCT. 33,34 No additional toxicities attributable to RIT compared with toxicities reported previously with this regimen without RIT were observed. 6 Toxicity observed within the first 180 days after transplantation was moderate with mainly Common Toxicity Criteria grade 2-3 toxicities.…”

Section: Dosimetrymentioning

confidence: 71%

Dose-escalated radioimmunotherapy as part of reduced intensity conditioning for allogeneic transplantation in patients with advanced high-grade non-Hodgkin lymphoma

Bethge

Harsdorf

Bornhäuser

et al. 2012

Bone Marrow Transplant

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A total of 20 patients enrolled in a multicenter phase II dose escalation study of radioimmunotherapy (RIT) using yttrium-90-ibritumomab tiuxetan at two dose levels (22 and 30 MBq/kg) in 10 patients, combined with reduced intensity conditioning (RIC) using fludarabine, melphalan and alemtuzumab followed by allogeneic hematopoietic cell transplantation (HCT) from either matched-related (n ¼ 5) or matched-unrelated donors (n ¼ 15). Postgrafting immunosuppression with cyclosporine was administered. Diagnoses were diffuse large B-cell lymphoma (n ¼ 13), transformed CLL (n ¼ 4), blastic mantle cell lymphoma (n ¼ 2) and follicular lymphoma grade 3 (n ¼ 1). Median age was 51 (range, 29-69) years. All patients were high risk with relapsed/ refractory disease or relapse after preceding autologous HCT. Median follow-up of patients alive was 1115 (range, 1006-1252) days. No directly RIT-related toxicities were observed. The cumulative incidence of non-relapse mortality was 30%. Incidences of grade II-IV acute and chronic GvHD was 45% and 70%, respectively. Kaplan-Meier estimated 3-year OS and EFS were 20% for both dose levels. In conclusion, dose escalation of RIT and combined use with RIC is feasible with no additional toxicity due to dose escalation. This study is registered on http://clinicaltrials.gov as NCT00302757.

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Section: Dosimetrymentioning

confidence: 71%

Dose-escalated radioimmunotherapy as part of reduced intensity conditioning for allogeneic transplantation in patients with advanced high-grade non-Hodgkin lymphoma

Bethge

Harsdorf

Bornhäuser

et al. 2012

Bone Marrow Transplant

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“…32,35 The median radiation exposure as calculated in 56 patients enrolled in the phase I/II studies was 13.7 cGy/mCi to liver, 9.8 cGy/mCi in the lungs and 1.5 cGy/mCi to the kidneys. 31,35 Hence the median liver exposure is in the range of 500 cGy and much less for other organs. The median bone marrow exposure was calculated to be less than 100 cGy.…”

Section: Radiation Kinetics and Safetymentioning

confidence: 99%

“…During the registrational clinical trials, a meticulous and thorough dosimetry procedure was performed largely using data derived from 111 In-ibritumomab tiuxetan ( 111 In-IT) kinetics. 31,32 The purpose of dosimetry was to eliminate the possibility of excessive radiation exposure of vital organs. Thus, pharmacokinetics and the biologic half-life based on repetitive blood sampling and total body counts were determined and an exponential or bi-exponential best-fit curve was constructed for each patient.…”

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confidence: 99%

Radioimmunotherapy for Non-Hodgkin Lymphoma : Historical Perspective and Current Status

Emmanouilides

2007

J Clin Exp Hematopathol

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90 Y-ibritumomab tiuxetan utilizes a monoclonal anti-CD20 antibody to deliver b-emitting yttium-90 to the malignant B-cells. Clinical trials have demonstrated its efficacy, which is largely independent of the intrinsic activity of the anti-CD20 antibody. A similar anti-CD20 radiotherapeutic compound, 131 I-tositumomab, was subsequently approved in the USA. The advantages of increased efficacy compared to the naked antibody are gained at the expense of myelotoxicity which is dose limiting but reversible. Studies exploring expanded applications of radioimmunotherapy have been recently completed or are under way. It is hoped that RIT will be an ideal agent for consolidation after chemotherapy for both indolent and aggressive non-Hodgkin lymphoma as well as a useful addition to preparatory high dose regimens prior to transplant. RIT has been shown to be an effective and clinically relevant complementary therapeutic approach for patients with lymphoma. 〔J Clin Exp Hematopathol 47(2) : 43-60, 2007〕

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“…Thus, electron transport plays little role in absorbed dose simulations when this isotope is used. Even for 90 Y, in which there has been significant recent interest as a radioimmunotherapy isotope [9]- [11], the maximum electron ranges corresponding to the β endpoint energy (2.28 MeV) and average energy (.94 MeV) are still only 1 cm and 4 mm, respectively, meaning that some of the speedup DPM achieves through its electron transport model will not be realized except for small voxel sizes. Further, in many cases, the resolution of SPECT images used for activity quantification may be of the same order as electron range, thus mandating large voxels and so virtually negating all of DPM's potential electron transport speedup.…”

Section: Introductionmentioning

confidence: 99%

Method for Fast CT/SPECT-Based 3D Monte Carlo Absorbed Dose Computations in Internal Emitter Therapy

Wilderman

Dewaraja

2007

IEEE Trans. Nucl. Sci.

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The DPM (Dose Planning Method) Monte Carlo electron and photon transport program, designed for fast computation of radiation absorbed dose in external beam radiotherapy, has been adapted to the calculation of absorbed dose in patient-specific internal emitter therapy. Because both its photon and electron transport mechanics algorithms have been optimized for fast computation in 3D voxelized geometries (in particular, those derived from CT scans), DPM is perfectly suited for performing patient-specific absorbed dose calculations in internal emitter therapy. In the updated version of DPM developed for the current work, the necessary inputs are a patient CT image, a registered SPECT image, and any number of registered masks defining regions of interest. DPM has been benchmarked for internal emitter therapy applications by comparing computed absorption fractions for a variety of organs using a Zubal phantom with reference results from the Medical Internal Radionuclide Dose (MIRD) Committee standards. In addition, the β decay source algorithm and the photon tracking algorithm of DPM have been further benchmarked by comparison to experimental data. This paper presents a description of the program, the results of the benchmark studies, and some sample computations using patient data from radioimmunotherapy studies using 131 I.

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Radioimmunotherapy of relapsed or refractory non-Hodgkin's lymphoma (NHL) with IDEC-Y2B8

Cited by 14 publications

References 0 publications

Dose-escalated radioimmunotherapy as part of reduced intensity conditioning for allogeneic transplantation in patients with advanced high-grade non-Hodgkin lymphoma

Dose-escalated radioimmunotherapy as part of reduced intensity conditioning for allogeneic transplantation in patients with advanced high-grade non-Hodgkin lymphoma

Radioimmunotherapy for Non-Hodgkin Lymphoma : Historical Perspective and Current Status

Method for Fast CT/SPECT-Based 3D Monte Carlo Absorbed Dose Computations in Internal Emitter Therapy

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