Journal of Clinical Oncology, Vol 18, Issue 6
(March), 2000: 1316-1323
© 2000 American Society for Clinical Oncology
Multicenter Phase II Study of Iodine-131 Tositumomab for Chemotherapy-Relapsed/Refractory Low-Grade and Transformed Low-Grade B-Cell Non-Hodgkin’s Lymphomas
By Julie M. Vose,
Richard L. Wahl,
Mansoor Saleh,
Ama Z. Rohatiner,
Susan J. Knox,
John A. Radford,
Andrew D. Zelenetz,
George F. Tidmarsh,
Robert J. Stagg,
Mark S. Kaminski
From the University of Nebraska Medical Center, Omaha, NE; University of Michigan Medical Center, Ann Arbor, MI; University of Alabama-Birmingham, Birmingham, AL; St Bartholomew’s Hospital, London; Christie Hospital National Health Service Trust, Manchester, England; Stanford University Medical Center, Palo Alto; Coulter Pharmaceutical, South San Francisco, CA; and Memorial Sloan-Kettering Cancer Center, New York, NY.
Address reprint requests to Julie M. Vose, MD, Department of Internal Medicine, 987680 Nebraska Medical Center, Omaha, NE 68198-7680.
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ABSTRACT
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PURPOSE: This multicenter phase II study evaluated the efficacy, dosimetry methodology, and safety of iodine-131 tositumomab in patients with chemotherapy-relapsed/refractory low-grade or transformed low-grade non-Hodgkin’s lymphoma (NHL).
PATIENTS AND METHODS: Patients received a dosimetric dose that consisted of 450 mg of anti-B1 antibody followed by 35 mg (5 mCi) of iodine-131 tositumomab. Serial total-body gamma counts were then obtained to calculate the patient-specific millicurie activity required to deliver the therapeutic dose. A therapeutic dose of 75 cGy total-body dose (attenuated to 65 cGy in patients with platelet counts of 101,000 to 149,000 cells/mm3) was given 7 to 14 days after the dosimetric dose.
RESULTS: Forty-five of 47 patients were treated with a single dosimetric and therapeutic dose. Twenty-seven patients (57%) had a response. The response rate was similar in patients with low-grade (57%) or transformed low-grade (60%) NHL. The median duration of response was 9.9 months. Fifteen patients (32%) achieved a complete response (CR; 10 CRs and five clinical CRs), including five patients (50%) with transformed low-grade NHL. The median duration of CR was 19.9 months, and six patients have an ongoing CR. Treatment was well tolerated, with the principal toxicity being hematologic. The most common nonhematologic toxicities that were considered to be possibly related to the treatment included mild to moderate fatigue (32%), nausea (30%), fever (26%), vomiting (15%), infection (13%), pruritus (13%), and rash (13%). Additionally, one patient developed human-antimouse antibodies.
CONCLUSION: Iodine-131 tositumomab produced a high overall response rate, and approximately one third of patients had a CR despite having chemotherapy-relapsed or refractory low-grade or transformed low-grade NHL.
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INTRODUCTION
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EXTERNAL-BEAM radiation therapy is the mainstay of treatment for patients with stage I/II low-grade B-cell non-Hodgkin’s lymphoma (NHL) and may potentially be curative. It remains controversial whether the addition of combination chemotherapy to radiation can improve these results.1 Unfortunately, most patients present with incurable stage III or IV disease. When treatment is initiated, patients are typically treated with single-agent or combination chemotherapy. Although most patients with advanced-stage low-grade NHL initially achieve a response with chemotherapy, relapse inevitably occurs. Patients who relapse after chemotherapy are usually treated with another course of single-agent therapy, a combination chemotherapy regimen, high-dose chemotherapy and hematopoietic stem-cell transplantation, and/or external-beam radiation for local symptoms.2 Typically, the response rate declines and the duration of response grows progressively shorter with each subsequent course of therapy.3 In addition, in approximately one third of patients, low-grade NHL transforms into a higher-grade histology that is associated with an accelerated rate of growth and a poorer prognosis. Unfortunately, none of the approaches used to date have improved survival4-6 and the treatments are often associated with significant adverse effects.7,8 Thus there is a need for newer therapies that produce long-term responses and less toxicity.
One novel approach to treatment has been the development of therapies that target specific tumor antigens or idiotypic regions of cell-surface immunoglobulin molecules. Because human B cells have unique cell-surface antigens and B-cell NHL is theoretically derived from a single clonal origin, early investigations focused on anti-idiotype antibodies.9,10 However, difficulties were encountered with respect to tumor heterogeneity, somatic mutation, and practical considerations (eg, the time and cost associated with individualized patient-specific antibodies). Thus lineage-specific antigens, such as the pan B-cell differentiation antigens CD19, CD20, or CD22, which are widely expressed on the surface of B cells, became the focus of immunotherapy-based treatments.11-14 Early trials with unlabeled antibodies directed against CD19 and CD21 produced disappointing results.13,14 However, rituximab, a chimeric antibody directed against the CD20 antigen, produced a response rate of 48% and a complete response (CR) rate of 6% in 166 patients with relapsed low-grade or follicular NHL.15
Radioimmunoconjugates have been developed in an attempt to take advantage of the antilymphoma effects of the antibody itself in conjunction with the additive local radiation effects. The proposed mechanisms of cytotoxicity of radioimmunoconjugates involve the cytotoxic effect of radiation and antibody-induced effects, such as apoptosis, antibody-dependent cellular cytotoxicity, and/or complement-dependent cytotoxicity.16-18
Iodine-131 tositumomab is a radiolabeled immunoglobulin G-2a murine monoclonal antibody that is specific to the CD20 antigen. Iodine-131 labeling allows for targeted delivery of beta radiation to antigen-positive malignant cells as well as to adjacent antigen-negative or nontargeted antigen-positive malignant cells, because beta emissions travel across several cell diameters (mean range, 0.4 mm) to radiate neighboring malignant cells.11,12 In addition, Iodine-131 produces gamma emissions that enable sequential total-body gamma counts to be obtained over time resulting in the ability to calculate the patient-specific millicurie activity required to deliver the desired therapeutic radiation dose.
A phase I/II dose-escalation trial of iodine-131 tositumomab was conducted in 59 patients with CD20 antigen-expressing B-cell NHL.19 The patients had received an average of four chemotherapy regimens, 36% had large tumor burdens, 51% had elevated plasma levels of lactate dehydrogenase, and 14 had experienced disease progression after autologous bone marrow transplantation. Dosimetric studies established that a predose of 475 mg of unlabeled anti-B1 antibody optimized the tumor–to–total-body ratio of radioactivity. The maximum-tolerated dose of iodine-131 tositumomab for patients who had not undergone a prior bone marrow transplantation was 75 cGy total-body dose (TBD). Forty-two (71%) of 59 patients had a response, and the median duration of response was 8.9 months. Twenty (34%) of 59 patients had a CR, and the median duration of CR was 18.3 months. Patients with low-grade or transformed disease had a higher response rate (83%) than those with de novo intermediate- or high-grade disease (41%). In addition, encouraging results have been reported with a myeloablative dose of iodine-131 tositumomab as conditioning therapy for bone marrow or stem-cell transplantation.20,21
The purpose of this phase II study was to assess the efficacy, dosimetry methodology, and safety of iodine-131 tositumomab therapy in a multicenter trial.
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PATIENTS AND METHODS
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This multicenter, phase II, single-arm, open-label study evaluated a single dosimetric and therapeutic dose of iodine-131 tositumomab (Coulter Pharmaceutical, Inc, South San Francisco, CA) in patients with chemotherapy-relapsed/refractory low-grade or transformed low-grade B-cell NHL. The study was conducted at five clinical sites in the United States and two in England. The protocol was approved by the institutional review board or ethics committee at each site, and all patients gave written informed consent before study entry.
Patient Eligibility
Patients enrolled onto this study were at least 18 years old and had a histologically confirmed diagnosis of CD-20 positive low-grade NHL as classified by the International Working Formulation for Clinical Usage criteria (International Working Formulation A, B, C) or transformed low-grade NHL. Patients were considered to have transformed low-grade NHL if they had an initial biopsy that was consistent with low-grade NHL and a subsequent biopsy that was consistent with transformation to a large-cell pattern of higher-grade NHL. All patients had been previously treated with at least one chemotherapy regimen containing an anthracycline or anthracenedione and had failed to respond to or experienced disease progression within 1 year of the completion their last chemotherapy regimen. In addition, patients had an anticipated survival of at least 3 months, a Karnofsky performance status of greater than 60%, an absolute granulocyte count of greater than 1,500 cells/mm3, platelet count of greater than 100,000 cells/mm3, serum creatinine of less than 2.0 mg/dL, and a total bilirubin of less than 2.0 mg/dL. All patients had bidimensionally measurable disease with no more than 25% of the intratrabecular marrow space involved with NHL.
Patients were excluded from the study if they had previously been treated with stem-cell transplantation, an unlabeled antibody, or radioimmunotherapy. Other exclusion criteria included the following: previous or current investigational drug use, evidence of obstructive hydronephrosis, active infection requiring intravenous (IV) antibiotics, or receipt of cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment within 4 weeks before study entry (6 weeks for nitrosourea). In addition, progressive disease arising within 1 year in a field previously irradiated with more than 35 Gy, previous allergic reactions to iodine (excluding IV contrast materials), pregnancy, and prior malignancy other than lymphoma unless disease-free for 5 years (except for cervical carcinoma-in-situ or adequately treated skin cancer) were also considered to be exclusion criteria.
Drug Administration and Dosimetry
Tositumomab was supplied by Coulter Pharmaceutical. Each site radiolabeled the anti-B1 antibody with iodine-131 using the Iodogen method22 and performed quality-control testing for immunoreactivity and purity. To block uptake of iodine-131 by the thyroid, patients received saturated solution of potassium iodide, two drops orally three times daily, beginning at least 24 hours before the first infusion of iodine-131 tositumomab (ie, the dosimetric dose) and continuing for 14 days after the therapeutic dose. Patients also received potassium perchlorate (200 mg orally three times daily for 7 days) starting on the day of the therapeutic infusion. Thirty minutes before the dosimetric and therapeutic dose, patients were premedicated with oral acetaminophen (650 mg) and diphenhydramine (50 mg). The dosimetric dose involved the IV administration of 450 mg of unlabeled tositumomab infused over approximately 1 hour followed by 5 mCi (35 mg) of iodine-131 tositumomab infused over 20 minutes.
Serial total-body sodium iodide (NaI) probe counts and whole-body gamma camera scans were obtained approximately 1 hour after the dosimetric infusion and daily for 7 days (Fig 1). Total-body gamma counts from the NaI probe measurements were used to determine the radioactive clearance from each patient and subsequently to determine the millicurie activity of iodine-131 tositumomab required to deliver the desired therapeutic dose of total-body radiation. The methodology for determining the patient-specific millicurie activity was performed in accordance with the Medical Internal Radiation Dose Primer for Absorbed Dose Calculations.23,24 On achieving concordance between the NaI probe counts and total-body gamma camera counts (r = 0.97), the study protocol was amended to use the gamma camera total-body counts for therapeutic dose determination.
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Fig 1. Treatment schema for this single-arm, open-label study. All patients received a dosimetric dose on day 0, serial total-body gamma counts by either NaI probe or gamma camera scans, and a therapeutic dose between study days 7 and 14.
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The therapeutic dose was administered 7 to 14 days after administration of the dosimetric dose. Patients were hospitalized for the administration of the therapeutic dose and were kept in isolation after the therapeutic dose until they were emitting  5 mrem/h of radiation, which generally occurred 3 to 4 days after administration of the therapeutic dose. Patients received an unlabeled predose of 450 mg of tositumomab infused over 1 hour followed by the patient-specific millicurie activity (35 mg) of iodine-131 tositumomab infused over 20 minutes. The desired TBD was 65 cGy for patients with a baseline platelet count of 100,001 to 149,999 cells/mm3 and 75 cGy for patients with a baseline platelet count  150,000 cells/mm3. The millicurie dose for the therapeutic dose was calculated on the basis of actual body weight for patients weighing 137% of their lean body weight and at 137% of the lean body weight for patients weighing more than 137% of their lean body weight. Vital signs were taken every 15 minutes during infusion of the antibody.
At three clinical sites, gamma camera scans were obtained daily for 7 days to perform organ and tumor dosimetry using MIRDOSE 3.1 software (RIDIC, Oakridge, TN). Regions of interest were drawn for organs and tumors, and, after correcting for attenuation and background, residence times were estimated from the resulting time-activity curves using a multiexponential model for radioactive clearance. Tumor and spleen sizes were determined from sequential computed tomography scans. Additionally, in these patients, blood and marrow dosimetry was performed from radioactivity counts of sequential blood samples.25
Response Criteria
Tumor response was assessed by physical examination and computed tomography at weeks 6 and 12, and then every 3 months for 2 years or until disease progression or death. In addition, for patients who had a positive baseline bone marrow biopsy, a repeat bone marrow biopsy was required to demonstrate the absence of lymphoma for a response of CR or clinical CR (CCR). All measurable and assessable disease was considered for response assessment. CR was defined as complete disappearance of all measurable and assessable disease. A CCR was characterized as complete disappearance of all tumor lesions, but with the examination precluding an unequivocal statement that the tumor completely disappeared. Partial response (PR) was defined as a 50% or greater reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions, with no new lesions developing. Stable disease was defined as less than 50% reduction and less than 25% increase in the sum of the products of the longest perpendicular diameters of measurable lesions, with no new lesions developing. Progressive disease was defined as a greater than 25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of the measurable lesions or the appearance of a new lesion. For purposes of summary, CR and CCR were combined and stated as total CR. A separate assessment of response by an independent review panel that was masked to the investigator’s response assessment was performed for all patients who achieved an investigator-assessed CR, CCR, or PR.
Evaluation of Toxicity
Adverse experiences were graded using the National Cancer Institute common toxicity criteria. Safety was assessed by physical examination and laboratory evaluations (eg, serum chemistries), which were obtained at baseline, weeks 6 and 12, every 3 months for 2 years, and every 6 months thereafter until disease progression or death. Serum chemistries also were evaluated at 2 days after administration of the therapeutic dose and at day 21. Complete blood counts, including differential and platelet counts, were obtained at baseline, 2 days before administration of the therapeutic dose, and weekly beginning 2 weeks after the therapeutic dose for 7 weeks or until a return to a consistent grade 0 hematologic toxicity was recorded; subsequent evaluations were performed at week 12, every 3 months for 2 years, and every 6 months thereafter.
Serum for analysis of human antimurine antibodies (HAMA) was collected before administration of the dosimetric dose, 2 days before the therapeutic dose, and at weeks 6, 12, and 24. Samples were assayed for HAMA using a centralized radioimmunoassay (data on file, Coulter Pharmaceutical). Quantitative serum immunoglobulins were obtained at baseline and at weeks 6, 12, and 24. Thyroid function tests were performed at baseline, at 6, 9, and 12 months, and every 6 months thereafter until disease progression or death.
Statistical Analysis
Analyses were performed using data from all patients (intent-to-treat) through January 10, 1999. The level of significance for all comparative analyses was set at .05, with exact confidence limits calculated from binomial distributions. All subgroup comparisons were performed with two-sided test statistics, and P values were presented without adjustment for multiple comparisons, multiple outcomes, or multiple looks. Data for duration of response were analyzed using the Kaplan-Meier method.26
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RESULTS
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Patient Characteristics
A total of 47 patients with low-grade or transformed low-grade B-cell NHL were enrolled onto this phase II study between December 5, 1995, and November 20, 1996. The median patient age was 49 years, with a range of 23 to 74 years (Table 1); 53% were male. Thirty-seven patients (79%) had a diagnosis of low-grade NHL, and 10 patients (21%) had a diagnosis of transformed low-grade NHL. The median time from initial diagnosis to study enrollment was 41 months. The median number of previous chemotherapy regimens was four (range, one to eight regimens). Twenty-two (47%) of 47 patients had achieved a response, and six (13%) of 47 had achieved a CR to their last chemotherapy regimen. The majority of patients (91%) had stage III or IV disease at study entry, with 44% of those evaluated (n = 39) having bulky disease (> 500 g) and 87% having two or more high-risk factors as defined by the International Prognostic Index.27 Additionally, 24 patients (51%) who entered the study had bone marrow involvement; 20 (43%) had platelet counts of less than 150,000 cells/mm3, and 13 (28%) had a hemoglobin level of less than 12 g/dL. Baseline serum immunoglobulin G was below normal in 45% of patients.
Dosing and Dosimetry
Forty-five patients (96%) received a single dosimetric and therapeutic dose of iodine-131 tositumomab per protocol. One patient with transformed low-grade NHL had rapidly progressive disease at enrollment and received only the dosimetric dose, and one patient did not receive the therapeutic dose at the protocol-specified time.
Each enrolling site was validated for performing dosimetry, and all of the site calculations for prescribed administered millicurie activity were reviewed by the reference center. All of the site calculations were within 10% of the activity calculated at the central dosimetry center. A graphical method was developed for the dosing methodology that was reproducible, easy to perform, and transferable to multiple institutions. The NaI probe and gamma camera measurements were found to give equivalent total-body clearance rates (r = 0.973). The total-body clearance of iodine-131 tositumomab was monoexponential and variable across patients. The mean half-life was 65.2 ± 12.5 hours by NaI probe count and 65.8 ± 12.9 hours by gamma camera. Thirty-six patients (77%) received total-body therapeutic doses of 75 cGy, nine patients (19%) received 65 cGy, one patient (2%) received 53 cGy, and one patient (2%) did not receive the therapeutic dose. The mean activity for all therapeutic doses administered was 88 mCi (range, 45 to 177 mCi). Normal organ doses were modest, with the kidneys, spleen, liver, bladder, and lungs receiving mean doses of 4.99, 3.83, 2.25, 2.14, and 1.83 Gy (at a rate of 75 cGy of TBD), respectively. These values fall well below normal tissue tolerance for external-beam radiotherapy,28 which is a conservative estimate for tolerance of normal organs compared with the low-dose rate with internally administered iodine-131 tositumomab therapy. On average, tumors received the highest doses of radiation, with a mean of 7.95 Gy per 75 cGy of TBD (10.6 times the mean TBD).
Response Rates and Duration
All investigator-assessed responses were confirmed by an independent panel masked to the investigators’ response assessment. On an intent-to-treat basis, a response (CR, CCR, or PR) was observed in 27 (57%) of 47 patients (Table 2); 27 (60%) of 45 patients who received a single dosimetric and therapeutic dose responded. The median duration of response was 9.9 months (95% confidence interval [CI], 4.5 to 17.3 months). The total CR rate (CR + CCR) was 15 (32%) of 47 patients, and a CR was observed in at least one patient at each of the clinical sites. The median duration of response for the complete responders was 19.9 months (95% CI, 14.3 months to upper limit not reached; Fig 2). Six patients have an ongoing CR, with durations ranging from 26.9+ to 33.8+ months. The median time to disease progression or death was 11.6 months (95% CI, 6.1 to 19.2 months) for patients who responded to therapy and 5.3 months (95% CI, 3.2 to 8.9 months) for all patients.
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Fig 2. Response duration after treatment with iodine-131 tositumomab therapy. The median duration of response for complete responders was 19.9 months (95% CI, 14.3 to upper limit not reached), whereas the median duration of response for all patients was 9.9 months (95% CI, 4.5 to 17.3 months).
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Similar results were observed in patients with low-grade NHL and transformed low-grade NHL (Table 2). A 57% response rate (CR, CCR, PR) was observed in the 37 patients who were diagnosed with low-grade NHL, which was comparable to the 60% response rate that was noted in the 10 patients with transformed low-grade NHL. The median duration of response was 8.2 months (95% CI, 4.4 to 19.9 months) in patients with low-grade NHL and 12.1 months (95% CI, 4.5 months to upper limit not reached) in the group with transformed disease. Ten patients (27%) with low-grade and five (50%) with transformed low-grade NHL achieved CR or CCR; the median durations of response were 25.5 and 14.3 months for the low-grade and transformed low-grade complete responders, respectively. Response rates for patients with poor prognostic factors at enrollment, such as bulky disease (> 500 g of tumor burden) or elevated lactate dehydrogenase, were found to be 59% and 50%, respectively.
Adverse Experiences
Infusions of the iodine-131 tositumomab were well tolerated, which is similar to previous reports.19,21 No adverse experiences were reported during 77 (83%)of the 93 infusions. More adverse experiences were reported with infusion of the dosimetric dose (30% of patients) than the therapeutic dose (5%), and all were mild (57% were grade 1; 43% were grade 2). An adjustment to the rate of infusion of the dosimetric or therapeutic dose was required for only four (4%) of 93 doses.
Forty-five (96%) of 47 patients experienced an adverse event, with 44 (94%) of 47 patients experiencing an event that was considered by the investigators to be possibly related to therapy. Typically, these events were transient and mild to moderate in severity (grade 1 or 2). The most common nonhematologic adverse experiences thought to be related to therapy were fatigue (32%), nausea (30%), fever (26%), vomiting (15%), infections (13%), pruritus (13%), and rash (13%) (Table 3).
The principal toxicity was hematologic toxicity. Five patients (11%) had a nadir platelet count of less than 10,000 cells/mm3 and two patients (4%) had absolute neutrophil counts of less than 100 cells/mm3. The median time to nadir for absolute neutrophil count (ANC), hemoglobin, and platelet count were 43, 48, and 36 days from the therapeutic dose, respectively. The median nadir value after the therapeutic dose for ANC, hemoglobin, and platelet count were 800 cells/mm3, 10.2 g/dL, and 43,000 cells/mm3, respectively. The median time from the therapeutic dose to recovery of ANC, hemoglobin, and platelet count to baseline hematologic toxicity grade was 82, 68, and 68 days, respectively. Twelve (26%) of 47 patients received a platelet transfusion, 10 patients (21%) received an RBC transfusion, and six patients (13%) received a colony-stimulating factor.
None of the 45 patients who received a single dosimetric and therapeutic dose of iodine-131 tositumomab and who were evaluated for HAMA developed a HAMA response. However, one patient who received three doses of anti-B1 antibody because of a site-radiolabeling failure at the time of the therapeutic dose became HAMA-positive after therapy.
Survival
Twenty (43%) of 47 patients have died, and the median survival duration from study entry was 36 months (95% CI, 28 to 36 months) (Fig 3). Fifteen deaths were due to progressive NHL, and none of the deaths were considered by the investigators to be attributable to the study drug.
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Fig 3. Overall duration of survival from time of study entry. The median survival from study entry was 36 months (95% CI, 28 to 36 months).
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DISCUSSION
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The majority of patients with indolent NHL present with extensive stage III or IV disease and are not considered to be curable with conventional therapy.4-6 The addition of interferon therapy to an anthracycline therapy in high-risk patients with follicular NHL has been associated with an improvement in time to treatment failure in some studies.29 Once the patient relapses from the initial induction therapy, either the same therapy or other salvage therapies can often produce another response, which is typically shorter than the first.7,8 A subgroup of patients whose disease has transformed from a follicular to a diffuse NHL often present with known adverse prognostic factors, have difficulty achieving a CR, and have a poorer outlook with conventional therapy.30 Because traditional approaches to the therapy of patients with relapsed and refractory follicular and transformed NHL have not produced good long-term results, newer biologic therapies have been tested in these lymphomas.
In this multicenter phase II study of iodine-131 tositumomab in 47 patients with relapsed or refractory low-grade or transformed low-grade B-cell NHL, the overall response (CR, CCR, and PR) was found to be 57%, with a median duration of 9.9 months. A CR was observed in 15 (32%) of 47 patients. Six of these 15 patients continue in CR, with an ongoing duration of response ranging from 26.9 to 33.8 months. All responses were verified by an independent review of radiographs. These data confirm earlier findings in a similar group of patients.31
The patients included in this study had a number of poor prognostic factors, with a majority having stage III or IV NHL (91%), bulky disease (44%), bone marrow involvement (51%), and two or more high-risk factors (87%). The patients were heavily pretreated, receiving a median of four prior chemotherapy regimens (range, one to eight regimens), at least one of which contained an anthracycline or anthracenedione. The majority of patients (53%) had not responded to their last chemotherapy regimens, and the duration of response for the 47% of patients who responded was only 4 months. Responses were noted in all subgroups and no significant differences in response rates were found for any of these variables. Prior resistance to chemotherapy did not preclude response to iodine-131 tositumomab, nor did the presence of bulky disease. Based on the responses observed in this study, the activity of iodine-131 tositumomab does not seem to be limited in refractory or bulky disease.
Treatment was well tolerated, with few infusion-related adverse experiences. More were reported with infusion of the dosimetric dose (30% of patients) than the therapeutic dose (5%), and all were mild (57% were grade 1; 43% were grade 2). Infusion rate adjustment was rarely required (4%). Toxicities were primarily hematologic in nature, with patients receiving platelet or RBC transfusions or colony-stimulating factors when necessary. One patient developed HAMA after treatment. This individual received three doses of anti-B1 antibody instead of two because of a site-radiolabeling failure on the day of therapeutic infusion.
Because individualization of the therapeutic dose is required for delivery of the appropriate amount of whole-body radiation, one of the goals of this study was to verify the dosing methodology used at each center. All dosimetry calculations were confirmed at a central dosimetry center that had extensive prior experience with iodine-131 tositumomab therapy. Each center was validated to perform their own dosimetry. All of the site calculations of the administered millicurie activity of iodine-131 were within 10% of the reference center calculations. During the study, the dosimetry measurement procedure was simplified; serial NaI gamma probe counts and total-body gamma camera counts resulted in equivalent dose estimates without a loss of accuracy. Although 85% of the therapeutic emissions from iodine-131 are beta particles, this radionuclide is also a gamma emitter, which allows accessible determination of radiation energy and exposure.
The promising results obtained in this study demonstrate that iodine-131 tositumomab can be safely and effectively administered using a simplified treatment procedure. Durable CRs have occurred after therapy in a population of patients with chemotherapy-relapsed or refractory low-grade or transformed low-grade NHL, adding a new approach to the therapeutic armamentarium for management of such patients. Options under exploration with this agent include single-dose therapy, multidose therapy, combined-modality therapy with cytotoxic agents, or use in conjunction with hematopoietic stem-cell transplantation. Recent changes in the Nuclear Regulatory Commission guidelines for patient release after therapy with radionuclides, particularly iodine-131, will allow for outpatient treatment at the dosages used in this study.32
Other investigations to evaluate the feasibility of iodine-131 tositumomab therapy as a front-line treatment for advanced low-grade lymphoma33 and compare unlabeled with radiolabeled iodine-131 tositumomab in patients with progressive chemotherapy-relapsed or refractory disease,34 in addition to combination studies with dose-intense chemotherapy as conditioning therapy for autologous stem-cell transplantation, are in progress. Results from these studies are eagerly awaited.
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REFERENCES
|
|---|
1.
Longo DL, DeVita VT, Jaffe E, et al: Lymphocytic lymphomas, in De Vita VT, Hellman S, Rosenberg SA (eds): Cancer: Principles and Practice of Oncology (ed 4). Philadelphia, PA,JB Lippincott, 1993, pp 1859-1927
2.
Reddy S, Saxena VS, Pellettiere EV, et al: Stage I and II non-Hodgkin’s lymphomas: Long-term results of radiation therapy. Int J Radiat Oncol Biol Phys 6:687-692, 1989
3.
Johnson PM, Rohatiner AS, Whelan JS, et al: Patterns of survival in patients with recurrent follicular lymphoma: A 20-year study from a single center. J Clin Oncol 13:140-147, 1995[Abstract/Free Full Text]
4.
Portlock CS, Rosenberg SA: No initial therapy for stage III and IV non-Hodgkin’s lymphomas of favorable histologic types. Ann Intern Med 90:10-13, 1979
5.
Horning SJ, Rosenberg SA: The natural history of initially untreated low-grade non-Hodgkin’s lymphoma. N Engl J Med 311:1471-1475, 1984[Abstract]
6.
Aisenberg AC: Coherent view of non-Hodgkin’s lymphoma. J Clin Oncol 13:2656-2675, 1995[Abstract]
7.
Bierman PJ, Vose JM, Anderson JR, et al: High-dose therapy with autologous hematopoietic rescue for follicular low-grade non-Hodgkin’s lymphoma. J Clin Oncol 15:445-451, 1997[Abstract/Free Full Text]
8.
Horning SJ: Treatment approaches to the low-grade lymphomas. Blood 83:881-897, 1994[Free Full Text]
9.
Brown SL, Miller RA, Horning SJ, et al: Treatment of B-cell lymphomas with anti-idiotype antibodies alone and in combination with alpha-interferon. Blood 73:651-661, 1989[Abstract/Free Full Text]
10.
Meeker TC, Lowder J, Maloney DG, et al: A clinical trial of anti-idiotype therapy for B-cell malignancy. Blood 65a:1349-1363, 1985[Abstract/Free Full Text]
11.
Liu SY, Press OW: The potential for immunoconjugates in lymphoma therapy. Oncol Clin North Am 11:987-1006, 1997
12.
Renner C, Trumper L, Pfreundschuh M: Monoclonal antibodies in the treatment of non-Hodgkin’s lymphoma: Recent results and future prospects. Leukemia 11:S55-S59, 1997 (suppl 2)
13.
Hale G, Dyer MJS, Clark MR, et al: Remission induction in non-Hodgkin’s lymphoma with the reshaped human monoclonal antibody CAMPATH-1H. Lancet 2:1394-1399, 1988[Medline]
14.
Press OW, Appelbaum F, Ledbetter JA, et al: Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B cell lymphomas. Blood 69:584-591, 1987[Abstract/Free Full Text]
15.
McLaughlin P, Grillo-Lopez A, Link BK, et al: Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: Half of patients respond to a four-dose treatment program. J Clin Oncol 16:2825-2833, 1998[Abstract]
16.
Buchsbaum DJ, Wahl RL, Normolle DP, et al: Therapy with unlabeled and 131-I-labeled pan-B-cell monoclonal antibodies in nude mice bearing Raji Burkitt’s lymphoma xenografts. Cancer Res 52:6476-6481, 1992[Abstract/Free Full Text]
17.
Dillman RO: Antibodies as cytotoxic therapy. J Clin Oncol 12:1497-1515, 1994[Abstract]
18.
Colcher D: Centralized radiolabeling of antibodies for radioimmunotherapy. Med 39:11S-13S, 1998 (suppl)
19.
Stagg R, Wahl RL, Estes J, et al: Phase I/II study of iodine-131 anti-B1 antibody for non-Hodgkin’s lymphoma (NHL): Final results. Proc Am Soc Clin Oncol 17:39a, 1998 (abstr 150)
20.
Press OW, Eary JF, Appelbaum FR, et al: Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support. Engl J Med 329:1219-1224, 1993[Abstract/Free Full Text]
21.
Press OW, Eary JF, Appelbaum FR, et al: Phase II trial of 131I-B1 (anti-CD20) antibody therapy with autologous stem cell transplantation for relapsed B-cell lymphomas. Lancet 346:336-340, 1995[Medline]
22.
Salacinski RP, McLean C, Sykes JEF, et al: Iodination of proteins, glycoproteins, and peptides using a solid-phase oxidizing agent 1,3,4,6-tetrachloro-3a-6a-diphenylglycouril (Iodogen). Anal Biochem 117:136-146, 1981[Medline]
23.
Loevinger R, Budinger TF, Watson EE: MIRD Primer for Absorbed Dose Calculations. Reston, VA,The Society of Nuclear Medicine Inc, 1988
24.
Wahl RL, Kroll S, Zasadny DR: Patient-specific whole-body dosimetry: Principles and a simplified method for clinical implementation. Med 39:14S-20S, 1998 (suppl)
25.
Sgouros G: Bone marrow dosimetry for radioimmunotherapy: Theoretical considerations. J Nucl Med 34:689-694, 1993[Abstract/Free Full Text]
26.
Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457-481, 1958
27.
The International Non-Hodgkin’s Lymphoma Prognostic Factors Project: A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med 329:987-994, 1993[Abstract/Free Full Text]
28.
Emami B, Lyman J, Brown A, et al: Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 21:109-122, 1991[Medline]
29.
Solal-Celigny P, Lepage E, Brousse N, et al: Doxorubicin-containing regimen with or without interferon alfa-2b for advanced follicular lymphomas: Final analysis of survival and toxicity in the Groupe d’Etude des Lymphomes Folliculaires 86 trial. J Clin Oncol 16:2332-2338, 1998[Abstract]
30.
Bastion Y, Sebban C, Berger F, et al: Incidence, predictive factors, and outcome of lymphoma transformation in follicular lymphoma patients. J Clin Oncol 15:1587-1594, 1997[Abstract]
31.
Kaminski MS, Zasadny KR, Francis IR, et al: Iodine-131 anti-B1 radioimmunotherapy for B-cell lymphoma. J Clin Oncol 14:1974-1981, 1996[Abstract/Free Full Text]
32.
Siegel JA: Revised nuclear regulatory commission regulations for release of patients administered radioactive materials: Outpatient Iodine-131 anti-B1 therapy. J Nucl Med 39:28S-33S, 1998 (suppl)
33.
Kaminski MS, Estes J, Regan D, et al: Front-line treatment of advanced B-cell low-grade lymphoma (LGL) with radiolabeled iodine I 131 tositumomab: Initial experience. Proc Am Soc Clin Oncol 16:15a, 1997 (abstr 51)
34.
Knox SJ, Goris ML, Davis TA, et al: Randomized controlled study of iodine I 131 tositumomab vs. unlabeled anti-B1 antibody in patients with chemotherapy refractory low-grade non-Hodgkin’s lymphoma (abstract). Presented at the poster session of the Am Soc Ther Radiol Oncol (ASTRO) 39th Annual Meeting, Orlando, FL, October 19-23, 1997
Submitted June 29, 1999;
accepted November 16, 1999.
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|
|
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[Full Text]
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|
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48(1):
150 - 157.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. K. Tan, R. W. Wassenaar, and W. Zeng
Collimator Selection, Acquisition Speed, and Visual Assessment of 131I-Tositumomab Biodistribution in a Phantom Model
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34(4):
224 - 227.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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Phase II Trial of CHOP Chemotherapy Followed by Tositumomab/Iodine I-131 Tositumomab for Previously Untreated Follicular Non-Hodgkin's Lymphoma: Five-Year Follow-Up of Southwest Oncology Group Protocol S9911
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24(25):
4143 - 4149.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Kaminski, J. A. Radford, S. A. Gregory, J. P. Leonard, S. J. Knox, S. Kroll, and R. L. Wahl
Re-Treatment With I-131 Tositumomab in Patients With Non-Hodgkin's Lymphoma Who Had Previously Responded to I-131 Tositumomab
J. Clin. Oncol.,
November 1, 2005;
23(31):
7985 - 7993.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. I. Fisher, M. S. Kaminski, R. L. Wahl, S. J. Knox, A. D. Zelenetz, J. M. Vose, J. P. Leonard, S. Kroll, S. J. Goldsmith, and M. Coleman
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J. Clin. Oncol.,
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23(30):
7565 - 7573.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Nademanee, S. Forman, A. Molina, H. Fung, D. Smith, A. Dagis, C. Kwok, D. Yamauchi, A.-L. Anderson, P. Falk, et al.
A phase 1/2 trial of high-dose yttrium-90-ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patients with poor-risk or relapsed non-Hodgkin lymphoma
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106(8):
2896 - 2902.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. H. Brouwers, W. C.A.M. Buijs, P. F.A. Mulders, P. H.M. de Mulder, W. J.M. van den Broek, C. Mala, E. Oosterwijk, O. C. Boerman, F. H.M. Corstens, and W. J.G. Oyen
Radioimmunotherapy with [131I]cG250 in Patients with Metastasized Renal Cell Cancer: Dosimetric Analysis and Immunologic Response
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11(19):
7178s - 7186s.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Baranowska-Kortylewicz, M. Abe, K. Pietras, Z. P. Kortylewicz, T. Kurizaki, J. Nearman, J. Paulsson, R. L. Mosley, C. A. Enke, and A. Ostman
Effect of Platelet-Derived Growth Factor Receptor-{beta} Inhibition with STI571 on Radioimmunotherapy
Cancer Res.,
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65(17):
7824 - 7831.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Leonard, M. Coleman, L. Kostakoglu, A. Chadburn, E. Cesarman, R. R. Furman, M. W. Schuster, R. Niesvizky, D. Muss, J. Fiore, et al.
Abbreviated Chemotherapy With Fludarabine Followed by Tositumomab and Iodine I 131 Tositumomab for Untreated Follicular Lymphoma
J. Clin. Oncol.,
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23(24):
5696 - 5704.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. V. Rao, G. Akabani, and D. A. Rizzieri
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3(3):
157 - 165.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
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11(14):
5215 - 5222.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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Assessment of treatment-related myelodysplastic syndromes and acute myeloid leukemia in patients with non-Hodgkin lymphoma treated with tositumomab and iodine I131 tositumomab
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June 15, 2005;
105(12):
4576 - 4582.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Kaminski, M. Tuck, J. Estes, A. Kolstad, C. W. Ross, K. Zasadny, D. Regan, P. Kison, S. Fisher, S. Kroll, et al.
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N. Engl. J. Med.,
February 3, 2005;
352(5):
441 - 449.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Horning, A. Younes, V. Jain, S. Kroll, J. Lucas, D. Podoloff, and M. Goris
Efficacy and Safety of Tositumomab and Iodine-131 Tositumomab (Bexxar) in B-Cell Lymphoma, Progressive After Rituximab
J. Clin. Oncol.,
February 1, 2005;
23(4):
712 - 719.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Vose, P. J. Bierman, C. Enke, J. Hankins, G. Bociek, J. C. Lynch, and J. O. Armitage
Phase I Trial of Iodine-131 Tositumomab With High-Dose Chemotherapy and Autologous Stem-Cell Transplantation for Relapsed Non-Hodgkin's Lymphoma
J. Clin. Oncol.,
January 20, 2005;
23(3):
461 - 467.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Z. Lin, M. A. Teitell, and G. J. Schiller
The Evolution of Antibodies into Versatile Tumor-Targeting Agents
Clin. Cancer Res.,
January 1, 2005;
11(1):
129 - 138.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Modak and N.-K. V. Cheung
Antibody-Based Targeted Radiation to Pediatric Tumors
J. Nucl. Med.,
January 1, 2005;
46(1_suppl):
157S - 163S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. A. Davis, M. S. Kaminski, J. P. Leonard, F. J. Hsu, M. Wilkinson, A. Zelenetz, R. L. Wahl, S. Kroll, M. Coleman, M. Goris, et al.
The Radioisotope Contributes Significantly to the Activity of Radioimmunotherapy
Clin. Cancer Res.,
December 1, 2004;
10(23):
7792 - 7798.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Leonard, M. Coleman, J. C. Ketas, A. Chadburn, R. Furman, M. W. Schuster, E. J. Feldman, M. Ashe, S. J. Schuster, W. A. Wegener, et al.
Epratuzumab, a Humanized Anti-CD22 Antibody, in Aggressive Non-Hodgkin's Lymphoma: Phase I/II Clinical Trial Results
Clin. Cancer Res.,
August 15, 2004;
10(16):
5327 - 5334.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G. Rajendran, D. R. Fisher, A. K. Gopal, L. D. Durack, O. W. Press, and J. F. Eary
High-Dose 131I-Tositumomab (Anti-CD20) Radioimmunotherapy for Non-Hodgkin's Lymphoma: Adjusting Radiation Absorbed Dose to Actual Organ Volumes
J. Nucl. Med.,
June 1, 2004;
45(6):
1059 - 1064.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.J. Davies, A.Z.S. Rohatiner, S. Howell, K.E. Britton, S.E. Owens, I.N. Micallef, D.P. Deakin, B.M. Carrington, J.A. Lawrance, S. Vinnicombe, et al.
Tositumomab and Iodine I 131 Tositumomab for Recurrent Indolent and Transformed B-Cell Non-Hodgkin's Lymphoma
J. Clin. Oncol.,
April 15, 2004;
22(8):
1469 - 1479.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Vose
Bexxar(R): Novel Radioimmunotherapy for the Treatment of Low-Grade and Transformed Low-Grade Non-Hodgkin's Lymphoma
Oncologist,
April 1, 2004;
9(2):
160 - 172.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Y. C. Wong, S. Shibata, L. E. Williams, C. S. Kwok, A. Liu, D. Z. Chu, D. M. Yamauchi, S. Wilczynski, D. N. Ikle, A. M. Wu, et al.
A Phase I Trial of 90Y-Anti-Carcinoembryonic Antigen Chimeric T84.66 Radioimmunotherapy with 5-Fluorouracil in Patients with Metastatic Colorectal Cancer
Clin. Cancer Res.,
December 1, 2003;
9(16):
5842 - 5852.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. E. Witzig, C. A. White, L. I. Gordon, G. A. Wiseman, C. Emmanouilides, J. L. Murray, J. Lister, and P. S. Multani
Safety of Yttrium-90 Ibritumomab Tiuxetan Radioimmunotherapy for Relapsed Low-Grade, Follicular, or Transformed Non-Hodgkin's Lymphoma
J. Clin. Oncol.,
April 1, 2003;
21(7):
1263 - 1270.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Buchsbaum and A. F. LoBuglio
Targeting of 125I-Labeled B Lymphocyte Stimulator
J. Nucl. Med.,
March 1, 2003;
44(3):
434 - 436.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Sgouros, S. Squeri, A. M. Ballangrud, K. S. Kolbert, J. B. Teitcher, K. S. Panageas, R. D. Finn, C. R. Divgi, S. M. Larson, and A. D. Zelenetz
Patient-Specific, 3-Dimensional Dosimetry in Non-Hodgkin's Lymphoma Patients Treated with 131I-anti-B1 Antibody: Assessment of Tumor Dose-Response
J. Nucl. Med.,
February 1, 2003;
44(2):
260 - 268.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Juweid
Radioimmunotherapy of B-Cell Non-Hodgkin's Lymphoma: From Clinical Trials to Clinical Practice
J. Nucl. Med.,
November 1, 2002;
43(11):
1507 - 1529.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. R. Colnot, G. J. Ossenkoppele, J. C. Roos, J. J. Quak, R. de Bree, P. K. Borjesson, P. C. Huijgens, G. B. Snow, and G. A. M. S. van Dongen
Reinfusion of Unprocessed, Granulocyte Colony-stimulating Factor-stimulated Whole Blood Allows Dose Escalation of 186Relabeled Chimeric Monoclonal Antibody U36 Radioimmunotherapy in a Phase I Dose Escalation Study
Clin. Cancer Res.,
November 1, 2002;
8(11):
3401 - 3406.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Ansell, K. M. Ristow, T. M. Habermann, G. A. Wiseman, and T. E. Witzig
Subsequent Chemotherapy Regimens Are Well Tolerated After Radioimmunotherapy With Yttrium-90 Ibritumomab Tiuxetan for Non-Hodgkin's Lymphoma
J. Clin. Oncol.,
September 15, 2002;
20(18):
3885 - 3890.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. W. Seldin
Techniques for Using Bexxar for the Treatment of Non-Hodgkin's Lymphoma*
J. Nucl. Med. Technol.,
September 1, 2002;
30(3):
109 - 114.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. O. Dillman
Radiolabeled Anti-CD20 Monoclonal Antibodies for the Treatment of B-Cell Lymphoma
J. Clin. Oncol.,
August 15, 2002;
20(16):
3545 - 3557.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. E. Witzig, L. I. Gordon, F. Cabanillas, M. S. Czuczman, C. Emmanouilides, R. Joyce, B. L. Pohlman, N. L. Bartlett, G. A. Wiseman, N. Padre, et al.
Randomized Controlled Trial of Yttrium-90-Labeled Ibritumomab Tiuxetan Radioimmunotherapy Versus Rituximab Immunotherapy for Patients With Relapsed or Refractory Low-Grade, Follicular, or Transformed B-Cell Non-Hodgkin's Lymphoma
J. Clin. Oncol.,
May 15, 2002;
20(10):
2453 - 2463.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Siegel, S. Kroll, D. Regan, M. S. Kaminski, and R. L. Wahl
A Practical Methodology for Patient Release After Tositumomab and 131I-Tositumomab Therapy
J. Nucl. Med.,
March 1, 2002;
43(3):
354 - 363.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Vose, B. C.-H. Chiu, B. D. Cheson, J. Dancey, and J. Wright
Update on Epidemiology and Therapeutics for Non-Hodgkin's Lymphoma
Hematology,
January 1, 2002;
2002(1):
241 - 262.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
A. M. Wu, G. J. Tan, M. A. Sherman, P. Clarke, T. Olafsen, S. J. Forman, and A. A. Raubitschek
Multimerization of a chimeric anti-CD20 single-chain Fv-Fc fusion protein is mediated through variable domain exchange
Protein Eng. Des. Sel.,
December 1, 2001;
14(12):
1025 - 1033.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. D. Cheson
Some Like It Hot!
J. Clin. Oncol.,
October 1, 2001;
19(19):
3908 - 3911.
[Full Text]
|
|
|
|
|
|
|
M. S. Kaminski, A. D. Zelenetz, O. W. Press, M. Saleh, J. Leonard, L. Fehrenbacher, T. A. Lister, R. J. Stagg, G. F. Tidmarsh, S. Kroll, et al.
Pivotal Study of Iodine I 131 Tositumomab for Chemotherapy-Refractory Low-Grade or Transformed Low-Grade B-Cell Non-Hodgkin's Lymphomas
J. Clin. Oncol.,
October 1, 2001;
19(19):
3918 - 3928.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. L. McCune, J. P. Gockerman, and D. A. Rizzieri
Monoclonal Antibody Therapy in the Treatment of Non-Hodgkin Lymphoma
JAMA,
September 12, 2001;
286(10):
1149 - 1152.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Huhn, C. von Schilling, M. Wilhelm, A. D. Ho, M. Hallek, R. Kuse, W. Knauf, U. Riedel, A. Hinke, S. Srock, et al.
Rituximab therapy of patients with B-cell chronic lymphocytic leukemia
Blood,
September 1, 2001;
98(5):
1326 - 1331.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Goel, S. Augustine, J. Baranowska-Kortylewicz, D. Colcher, B. J. M. Booth, G. Pavlinkova, M. Tempero, and S. K. Batra
Single-Dose versus Fractionated Radioimmunotherapy of Human Colon Carcinoma Xenografts Using 131I-labeled Multivalent CC49 Single-chain Fvs
Clin. Cancer Res.,
January 1, 2001;
7(1):
175 - 184.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
O. W. Press, J. P. Leonard, B. Coiffier, R. Levy, and J. Timmerman
Immunotherapy of Non-Hodgkin's Lymphomas
Hematology,
January 1, 2001;
2001(1):
221 - 240.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. P. Treon, P. Maimonis, D. Bua, G. Young, N. Raje, J. Mollick, D. Chauhan, Y.-T. Tai, T. Hideshima, Y. Shima, et al.
Elevated soluble MUC1 levels and decreased anti-MUC1 antibody levels in patients with multiple myeloma
Blood,
November 1, 2000;
96(9):
3147 - 3153.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Hainsworth
Monoclonal Antibody Therapy in Lymphoid Malignancies
Oncologist,
October 1, 2000;
5(5):
376 - 384.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
T. A. Waldmann, R. Levy, and B. S. Coller
Emerging Therapies: Spectrum of Applications of Monoclonal Antibody Therapy
Hematology,
January 1, 2000;
2000(1):
394 - 408.
[Abstract]
[Full Text]
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TOP
ABSTRACT
INTRODUCTION
