Radiation dosimetry results and safety correlations from 90Y-ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory non-Hodgkin's lymphoma: combined data from 4 clinical trials.

Ibritumomab tiuxetan is an anti-CD20 murine IgG1 kappa monoclonal antibody (ibritumomab) conjugated to the linker-chelator tiuxetan, which securely chelates (111)In for imaging or dosimetry and (90)Y for radioimmunotherapy (RIT). Dosimetry and pharmacokinetic data from 4 clinical trials of (90)Y-ibritumomab tiuxetan RIT for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) were combined and assessed for correlations with toxicity data. METHODS: Data from 179 patients were available for analysis. Common eligibility criteria included <25% bone marrow involvement by NHL, no prior myeloablative therapy, and no prior RIT. The baseline platelet count was required to be > or = 100,000 cells/mm(3) for the reduced (90)Y-ibritumomab tiuxetan administered dose (7.4-11 MBq/kg [0.2-0.3 mCi/kg]) or > or = 150,000 cells/mm(3) for the standard (90)Y-ibritumomab tiuxetan administered dose (15 MBq/kg [0.4 mCi/kg]). Patients were given a tracer administered dose of 185 MBq (5 mCi) (111)In-ibritumomab tiuxetan on day 0, evaluated with dosimetry, and then a therapeutic administered dose of 7.4-15 MBq/kg (0.2-0.4 mCi/kg) (90)Y-ibritumomab tiuxetan on day 7. Both ibritumomab tiuxetan administered doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B-cells and improve ibritumomab tiuxetan biodistribution. Residence times for (90)Y in blood and major organs were estimated from (111)In biodistribution, and the MIRDOSE3 computer software program was used, with modifications to account for patient-specific organ masses, to calculate radiation absorbed doses to organs and red marrow. RESULTS: Median radiation absorbed doses for (90)Y were 7.42 Gy to spleen, 4.50 Gy to liver, 2.11 Gy to lung, 0.23 Gy to kidney, 0.62 Gy (blood-derived method) and 0.97 Gy (sacral image-derived method) to red marrow, and 0.57 Gy to total body. The median effective blood half-life was 27 h, and the area under the curve (AUC) was 25 h. No patient failed to meet protocol-defined dosimetry safety criteria and all patients were eligible for treatment. Observed toxicity was primarily hematologic, transient, and reversible. Hematologic toxicity did not correlate with estimates of red marrow radiation absorbed dose, total-body radiation absorbed dose, blood effective half-life, or blood AUC. CONCLUSION: Relapsed or refractory NHL in patients with adequate bone marrow reserve and <25% bone marrow involvement by NHL can be treated safely with (90)Y-ibritumomab tiuxetan RIT on the basis of a fixed, weight-adjusted dosing schedule. Dosimetry and pharmacokinetic results do not correlate with toxicity.     

Treatment of non-Hodgkin's lymphoma (NHL) with radiolabeled antibodies (mAbs)

Most patients with non-Hodgkin's lymphoma (NHL) achieve remission but, despite newer drugs, the natural history of this disease has not improved during the last 20 years. Less than one half of patients with aggressive NHL are cured, and few of those with low-grade NHL are curable. Furthermore, NHL becomes progressively more chemoresistant while remaining responsive to external beam radiation therapy. Radioimmunotherapy (RIT) is a logical strategy for the treatment of NHL because this disease is multifocal and radiosensitive. Because of their remarkable effectiveness for RIT, 2 anti-CD20 monoclonal antibodies (mAbs), one labeled with (111)In for imaging or (90)Y for therapy and a second labeled with (131)I for imaging and therapy, have been approved for use in patients with NHL. These drugs have proven remarkably effective and safe. Evidence for the importance of the radionuclide is manifested by the data in the randomized pivotal phase III trial of (90)Y-ibritumomab that revealed response rates were several times greater in the (90)Y-ibritumomab arm than in the rituximab arm. A second drug for RIT, (131)I-tositumomab, was compared in a pivotal trial with the efficacy of the last chemotherapy received by each patient. Once again, response rates were much higher for RIT. Both (90)Y-ibritumomab and (131)I-tositumomab require preinfusion of several hundred milligrams of unlabeled anti-CD20 mAb to obtain "favorable" biodistribution, that is, targeting of NHL. Response rates for other mAbs and radionuclides in NHL also have been high but these drugs have not reached the approval stage. These drugs can be used safely by physicians who have suitable training and judgment. Unlike chemotherapy, RIT is not associated with mucositis, hair loss, or persistent nausea or vomiting. Although hematologic toxicity is dose limiting, hospitalization for febrile neutropenia is uncommon. Randomized trials of RIT in different formulations have not been conducted, but there is evidence to suggest that the mAb, antigen, radionuclide, chelator, linker, and dosing strategy may make a difference in the outcome.     

Radioimmunotherapy with 131I-Rituximab in a Patient with Diffuse Large B-Cell Lymphoma Relapsed After Treatment with 90Y-Ibritumomab Tiuxetan

We report a case that demonstrates the efficacy of radioimmunotherapy (RIT) with radioiodinated rituximab (¹³¹I-rituximab) for relapsed diffuse large B-cell lymphoma (DLBCL). A 79-year-old male patient with DLBCL initially achieved a complete response (CR) after six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. However, the lymphoma relapsed 20 months later. Although the patient had achieved a second and a third CR after two cycles of ⁹⁰Y-ibritumomab tiuxetan, he experienced a third relapse approximately 3 years later. Between March and June 2011, the patient received three cycles of ¹³¹I-rituximab. Although he had achieved partial response after the second cycle, the disease progressed after the third cycle, and the total progression–free survival was thus 5 months. The patient suffered only relatively mild toxicity (grade 1 thrombocytopenia) during treatment. RIT with ¹³¹I-rituximab is therefore potentially effective in patients with relapsed DLBCL, even after the failure of ⁹⁰Y-ibritumomab tiuxetan therapy.     

Administration guidelines for radioimmunotherapy of non-Hodgkin's lymphoma with (90)Y-labeled anti-CD20 monoclonal antibody.

90Y-ibritumomab tiuxetan is a novel radioimmunotherapeutic agent recently approved for the treatment of relapsed or refractory low-grade, follicular, or CD20+ transformed non-Hodgkin's lymphoma (NHL). (90)Y-ibritumomab tiuxetan consists of a murine monoclonal antibody covalently attached to a metal chelator, which stably chelates (111)In for imaging and (90)Y for therapy. Both health care workers and patients receiving this therapy need to become familiar with how it differs from conventional chemotherapy and what, if any, safety precautions are necessary. Because (90)Y is a pure beta-emitter, the requisite safety precautions are not overly burdensome for health care workers or for patients and their families. (90)Y-ibritumomab tiuxetan is dosed on the basis of the patient's body weight and baseline platelet count; dosimetry is not required for determining the therapeutic dose in patients meeting eligibility criteria similar to those used in clinical trials, such as <25% lymphomatous involvement of the bone marrow. (111)In- and (90)Y-ibritumomab tiuxetan are labeled at commercial radiopharmacies and delivered for on-site dose preparation and administration. Plastic and acrylic materials are appropriate for shielding during dose preparation and administration; primary lead shielding should be avoided because of the potential exposure risk from bremsstrahlung. Because there are no penetrating gamma-emissions associated with the therapy, (90)Y-ibritumomab tiuxetan is routinely administered on an outpatient basis. Furthermore, the risk of radiation exposure to patients' family members has been shown to be in the range of background radiation, even without restrictions on contact. There is therefore no need to determine activity limits or dose rate limits before patients who have been treated with (90)Y radioimmunotherapy are released, as is necessary with patients who have been treated with radiopharmaceuticals that contain (131)I. Standard universal precautions for handling body fluids are recommended for health care workers and patients and their family members after (90)Y-ibritumomab tiuxetan administration. In summary, (90)Y-ibritumomab tiuxetan introduces (90)Y into clinical practice and expands the role nuclear medicine plays in the care of patients with cancer. Understanding the unique properties of this novel radioimmunoconjugate will facilitate its safe and effective use.     

Comparison of 90Y-ibritumomab tiuxetan and 131I-tositumomab in clinical practice.

We retrospectively evaluated our single-center clinical experience with (90)Y-ibritumomab tiuxetan and (131)I-tositumomab for therapy of refractory non-Hodgkin's lymphoma (NHL). We evaluated the hypothesis that the patient-specific dosing regimen used with (131)I-tositumomab results in less bone marrow toxicity than does the weight-based dosing regimen used with (90)Y-ibritumomab tiuxetan. METHODS: Thirty-eight patients (25 male and 13 female; median age, 64 y) received radioimmunotherapy for NHL (20 received (90)Y-ibritumomab tiuxetan; 18 received (131)I-tositumomab). Patient and disease characteristics were evaluated to determine whether any were prognostic indicators of short- or long-term clinical response. The 12-wk response rate and clinical and hematologic toxicities attributable to each therapy were assessed. The response rate at 12 wk was correlated with long-term overall survival. RESULTS: Twenty-six patients received full-radiation-dose radioimmunotherapy and 12 received attenuated doses because of hematologic concerns. The 12-wk overall response rate for all patients was 47%, and the complete response rate was 13%. The 12-wk overall response rate did not significantly differ between the (90)Y-ibritumomab tiuxetan and (131)I-tositumomab groups. Responses at 12 wk were more frequent in patients with normal levels of serum lactate dehydrogenase, no bone marrow involvement, and International Prognostic Index scores of no more than 2 (P < or = 0.04). Grade 3 or 4 thrombocytopenia occurred in 57% and 56% of patients treated with (90)Y-ibritumomab tiuxetan and (131)I-tositumomab, respectively. Grade 3 or 4 neutropenia was observed in 57% and 50%, respectively. The time to the absolute neutrophil count nadir was shorter for the (90)Y-ibritumomab tiuxetan group than for the (131)I-tositumomab group (36 +/- 9 vs. 46 +/- 14 d, P = 0.01). The mean percentage decline in platelet count after radioimmunotherapy was greater in the (90)Y-ibritumomab tiuxetan group than in the (131)I-tositumomab group (79% +/- 17% vs. 63% +/- 28%, P = 0.04). Overall survival was longer in responders than in nonresponders 12 wk after therapy (P < or = 0.05). CONCLUSION: Both (90)Y-ibritumomab tiuxetan and (131)I-tositumomab were well tolerated. We observed response rates at the lower range of those reported in the literature, possibly because of referral bias, dose attenuation, and reasonably liberal acceptance criteria for a patient to receive therapy. Initial response assessments 12 wk after radioimmunotherapy predict longer-term response. (131)I-tositumomab caused significantly less severe declines in platelet counts than did (90)Y-ibritumomab tiuxetan and may be a more appropriate choice for patients with limited bone marrow reserve, but large, randomized, prospective trials are needed to better compare the performance of these 2 treatments.     

Radioimmunotherapy for non-Hodgkin lymphoma: historical development and current status

Radioimmunotherapy treatment for lymphoma is a novel targeted therapeutic approach. Several years of development of radioimmunotherapeutic compounds came to fruition in February of 2002 when 90Y-ibritumomab tiuxetan (Zevalin, Y2B8) was approved in the USA and later in Europe, for the treatment of relapsed or refractory, low grade or transformed B-cell lymphoma in the USA. 90Y-ibritumomab tiuxetan utilizes a monoclonal anti-CD20 antibody to deliver beta-emitting yttrium-90 to the malignant B-cells. Clinical trials have demonstrated its efficacy, with observed clinical responses in the 80 % range. This product has become available in Europe, with simplified administration, for the treatment of relapsed follicular lymphoma. A similar anti-CD20 radiotherapeutic compound, 131I-tositumomab, was subsequently approved in the USA. Promising studies exploring expanded applications of radioimmunotherapy as consolidation, as part of transplant, or in other histologic types have been recently completed or are under way. Radioimmunotherapy has been shown to be an effective and clinically relevant complementary therapeutic approach for patients with lymphoma, bringing the Nuclear Medicine into lymphoma therapeutics.     

Feasibility of bremsstrahlung dosimetry for direct dose estimation in patients undergoing treatment with <Superscript>90</Superscript>Y-ibritumomab tiuxetan

Purpose  

Radioimmunotherapy with ⁹⁰Y-ibritumomab tiuxetan has been used successfully used in the treatment of CD20-positive non-Hodgkin’s lymphoma (NHL). Pretherapy imaging with ¹¹¹In-ibritumomab tiuxetan has been used in provisional dosimetry studies. Posttherapy imaging of ⁹⁰Y-ibritumomab tiuxetan for clinical use is appealing as it would simplify the data acquisition process and allow measurements of actual doses absorbed during treatment.     

Unsuspected Pneumonia Detected by Increased Lung Uptake on 111In-Ibritumomab Tiuxetan Scan

ABSTRACT: Y-ibritumomab tiuxetan (Zevalin) is a CD20-targeted radioimmunotherapy for the treatment of B-cell non-Hodgkin lymphoma approved by the FDA in 2002. The acquisition of an In ibritumomab tiuxetan scan (bioscan) to confirm normal biodistribution before treatment with Y-ibritumomab tiuxetan was initially required in the United States until November 2011. This is the first documented example of abnormal biodistribution due to unsuspected pneumonia detected by increased lung uptake on the bioscan. The pneumonia was treated and resolved before Y Zevalin, avoiding potential harm and indicating that a screening chest x-ray may be appropriate when a bioscan is not performed.     

The role of imaging with (111)In-ibritumomab tiuxetan in the ibritumomab tiuxetan (zevalin) regimen: results from a Zevalin Imaging Registry.

The ibritumomab tiuxetan therapeutic regimen consists of a dose of rituximab, 250 mg/m(2), followed by (111)In-ibritumomab tiuxetan, for imaging, on day 1 and a dose of rituximab followed by (90)Y-ibritumomab tiuxetan, for therapy, on day 7, 8, or 9. Treatment with the Food and Drug Administration-approved regimen also requires that scans be performed at 2-24 h and at 48-72 h after the (111)In-ibritumomab tiuxetan, with an optional third scan at 90-120 h, to confirm appropriate biodistribution. In the clinical trials before the approval of the regimen, only 1 patient (of approximately 400) was not treated with (90)Y-ibritumomab tiuxetan after imaging with (111)In-ibritumomab tiuxetan, because of altered biodistribution. The Zevalin Imaging Registry was established by Biogen Idec Inc. to identify cases of potential altered biodistribution and to collect clinical information in cases in which the regimen was not completed after imaging. METHODS: The registry surveyed treating physicians to verify completion of treatment with the ibritumomab tiuxetan therapeutic regimen in patients treated with (111)In-ibritumomab tiuxetan between March 27, 2002, and March 31, 2003. RESULTS: Survey data were collected on 953 of an estimated 1,144-1,192 patients in whom ibritumomab tiuxetan therapy was initiated (case capture rate of 80%-83%). Thirty-eight cases were reported in which a decision not to treat was made after imaging with (111)In-ibritumomab tiuxetan (4.0% of all cases captured); 16 of these were for imaging reasons, and 22 were for medical reasons. Twelve of the 16 imaging cases met the criteria for altered biodistribution (1.3%). Of these 12 cases, 6 (0.6%) were suspected to be true altered biodistribution and 6 appeared to be due to the use of a procedure for radiolabeling (111)In-ibritumomab tiuxetan that differed from that in the prescribing information. All cases of altered biodistribution were seen on the first image (2-24 h) after the administration of (111)In-ibritumomab tiuxetan. The 22 cases in which decisions not to treat were made for medical reasons accounted for 2.3% of the cases. The majority of these cases (19/22) were in patients who had an expected biodistribution but had a rapid change in their clinical condition that precluded treatment. CONCLUSION: The rate of true altered biodistribution was 0.6% in the Zevalin Imaging Registry, which collected treatment decisions based on data from approximately 80% of all patients treated commercially in the first year after drug approval. All cases of altered biodistribution were apparent on the first image, obtained at 2-24 h after the administration of (111)In-ibritumomab tiuxetan.     

Current status of cancer therapy with radiolabeled monoclonal antibody

Molecular targeting therapy has become a relevant therapeutic strategy for cancer. There are several monoclonal antibodies used for the treatment of malignant tumors. Radioimmunoconjugate is composed of antibody and radionuclide showing a synergistic effect of radiation and immunemediated cellular toxicity and thereby enabling increased efficacy and minimizing toxicity. Radioimmunotherapy using 131I- and 90Y-labeled anti-CD20 monoclonal antibodies is now indicated for the treatment of patients with CD20 antigen-expressing relapsed or refractory, low-grade or transformed non-Hodgkin's lymphoma (NHL), including patients who are refractory to anti-CD20 monoclonal antibody (rituximab) therapy in the United States. It has been exhibiting favorable anti-tumor efficacy in patients with NHL as compared with rituximab. Myelosuppression is the main side effect associated with the radioimmunotherapy but is usually reversible, and nonhematologic adverse reactions are mild to moderate. Following the impressive results of therapy using radiolabeled monoclonal antibodies for NHL, radioimmunotherapy for solid tumors has been examined; however, the results were unfavorable and did warrant further clinical trials as a single agent. Future studies on radioimmunotherapy for solid tumors should focus on the new strategies of targeting such as locoregional administration for intraperitoneal dissemination, and combination therapy with chemotherapy or cytostatic therapy. Although radioimmunotherapy for NHL has shown excellent results comparable to aggressive chemotherapy without severe adverse effects, additional clinical trials should be performed to define the proper role of radioimmunoconjugates as a relevant strategy for cure of NHL.     

放射性核素标记抗CD20单克隆抗体治疗B细胞淋巴瘤的研究进展

放射免疫治疗(radioimmunotherapy,RIT)属于内照射治疗,可以用较少的单克隆抗体耦联放射性核素,在肿瘤局部产生足够的电离辐射生物学效应,达到高效低毒的治疗效果。B细胞淋巴瘤有较高的复发比例,其CD20抗原表达率达90%以上,且不易从细胞膜上脱落,因此131I-利妥昔单抗CD20是B细胞淋巴瘤放免治疗的最佳靶点。目前已有数个放免治疗的药物,如:131I-托西莫单抗(131I-tositumomab)、131I-Rituximab、90Y-替坦异贝莫单抗(90Y-ibritumomabtiuxetan)等,用于B细胞淋巴瘤的临床治疗,它们具有各自的优缺点。使用结果表明:肿瘤部位的高吸收剂量保证了治疗的有效性,其对非靶器官的照射剂量是安全的。最主要的副反应包括:血小板减少症、中性粒细胞减少症、胃肠道反应及甲状腺功能减低症。在取得满意结果的同时,B细胞淋巴瘤放免治疗仍存在许多问题,人们正致力于更进一步的研究解决此类问题,以取得更好的治疗效果。     

肿瘤放射免疫疗法研究进展

放射免疫治疗是将针对肿瘤特异抗原的单克隆抗体用核素标记后,对肿瘤细胞进行的靶向治疗。在非霍奇金淋巴瘤的临床治疗中,放射免疫治疗已经成为一种常规的治疗手段。在实体瘤中,因为核素标记的单克隆抗体的定位很有限,所以限制了该疗法的使用。虽然如此,放射性核素标记的抗体在治疗微小病灶中的应用前景看好。     

Radioimmunotherapy with yttrium-90 ibritumomab tiuxetan. Clinical considerations, radiopharmacy, radiation protection, perspectives

90Y-ibritumomab tiuxetan (Zevalin) is currently approved for radioimmunotherapy of patients with relapsed or refractory follicular non-Hodgkin's lymphoma pretreated with rituximab. Future directions are the combined use of 90Y-ibritumomab tiuxetan as part of the initial treatment and as first-line multi-agent therapy of relapsed disease. Current studies investigate patients with other than follicular indolent histologies, e. g. diffuse large cell lymphoma. Labelling of 90Y ibritumomab tiuxetan is a safe procedure, the radiochemical purity is not disturbed by a higher room temperature or by metallic impurity. Quality control is recommended by thin layer chromatography (TLC), strips >15 cm are favourable. TLC cannot distinguish between the correctly radiolabelled antibodies and radiocolloid impurity. If necessary, additional HPLC should be performed. Radiocolloid impurities are absorbed to the solid phase and do not reach the eluate. If the radiochemical purity test is insufficient (<95%), the additional cleaning using EconoPac 10 DG columns (Biorad, Hercules, CA, USA) is a reliable procedure to reduce the percentage of free radionuclide. However, this procedure is not part of the approval.     

Biodistribution,radiation dosimetry and scouting of <Superscript>90</Superscript>Y-ibritumomab tiuxetan therapy in patients with relapsed B-cell non-Hodgkin’s lymphoma using <Superscript>89</Superscript>Zr-ibritumomab tiuxetan and PET

Purpose  

Positron emission tomography (PET) with ⁸⁹Zr-ibritumomab tiuxetan can be used to monitor biodistribution of ⁹⁰Y-ibritumomab tiuxetan as shown in mice. The aim of this study was to assess biodistribution and radiation dosimetry of ⁹⁰Y-ibritumomab tiuxetan in humans on the basis of ⁸⁹Zr-ibritumomab tiuxetan imaging, to evaluate whether co-injection of a therapeutic amount of ⁹⁰Y-ibritumomab tiuxetan influences biodistribution of ⁸⁹Zr-ibritumomab tiuxetan and whether pre-therapy scout scans with ⁸⁹Zr-ibritumomab tiuxetan can be used to predict biodistribution of ⁹⁰Y-ibritumomab tiuxetan and the dose-limiting organ during therapy.     

Radioimmunotherapy of B-cell non-Hodgkin's lymphoma.

In the past decade, several new antibody-based therapies - using either radiolabelled or unlabelled monoclonal antibodies - have become available for the treatment of patients with refractory or recurrent non-Hodgkin's lymphoma (NHL). Unlabelled monoclonal antibodies (mAbs) kill lymphoma cells by activating host immune effector mechanisms, or by inducing apoptosis. These mAbs can also be used to guide radionuclides to the lymphoma. This radioimmunotherapy (RIT) has been studied with various nuclides (131I, 90Y, 67Cu and 186Re) and with various mAbs. In this review the radionuclides, methods of dosing and recent RIT studies in patients with B-cell NHL are reviewed. Most of these studies demonstrate that RIT is an effective new treatment modality for NHL.     

非霍奇金淋巴瘤的CD20分子显像及靶向治疗研究进展

应用放射性核素标记B淋巴细胞分化抗原CD20单抗或其重组片段,在分子水平实现对非霍奇金淋巴瘤(NHL)显像和治疗,这将成为提高患者生存率的有效手段.该文介绍了CD20表面抗原的生物学特性及NHL抗CD20单抗的免疫治疗、放射免疫治疗以及放射免疫显像的研究进展.     

Serum sickness in a patient with follicular lymphoma after rituximab and radioimmunotherapy with ibritumomab tiuxetan

A previously healthy 47-year-old woman was treated for follicular lymphoma, grade III, with cyclophosphamide, adriamycin, vincristine, prednisone with rituximab (CHOP-R) followed by ibritumomab tiuxetan and rituximab. She developed a serum sickness-like illness during immunotherapy with fever, myalgias, arthralgias, and pleural and pericardial effusions. Despite anti-inflammatory therapies her symptoms persisted for 10 months before ultimate resolution. Her clinical course and literature are reviewed.     

Radioimmunoimaging and radioimmunotherapy: will these be routine procedures?

Despite major progress made during the past 25 years in the genetic engineering and labeling of monoclonal antibodies (Mab) and in the understanding of the uptake and kinetics of radiolabeled Mab by normal and tumor tissues, immunoscintigraphy never succeeded in becoming a routine procedure, compared with a bone or gallium scan. The more and more generalized availability of positron emission tomography (PET) with Fluorine-18 fluorodeoxyglucose (FDG) for diagnosis and staging of malignant diseases will probably definitively seal the fate of radioimmunodiagnosis as it has been conceived up until now. With respect to the nonspecificity of deoxyglucose uptake by tumor cells, it is not to be excluded that antibodies, or more likely antibody fragments, labeled with positron emitters might be used for tissue characterization. The recent success of radioimmunotherapy, especially in B-cell malignancies, entitles us to expect that RIT will become part of standard therapy of patients with malignancies. In that case, immunoscintigraphy will be needed for treatment planning (patient selection and dosimetry). One might even speculate that the oncologists who are becoming familiar with nuclear medicine tracer techniques for pretreatment evaluation might be interested in extending them to distribution and kinetic studies of other cytotoxic drugs. The close cooperation between nuclear medicine specialists, oncologists, and hematologists is essential to make radioimmunotherapy a routine procedure.     

90Y-ibritumomab tiuxetan in the treatment of relapsed or refractory B-cell non-Hodgkin's lymphoma

OBJECTIVE: Non-Hodgkin's lymphoma (NHL) is the most frequently diagnosed malignancy of the immune system, with more than 53,900 new cases diagnosed in 2002. Conventional cancer therapies cure many, but not the majority of, cases of the aggressive forms of NHL, and the more indolent and follicular forms of the disease that affect nearly half of all patients with NHL are considered incurable. In the absence of cure or survival benefits, treatments such as radioimmunotherapy that induce remission and prolong time off therapy are considered valuable. (90)Y-Ibritumomab tiuxetan recently became the first radioimmunotherapy agent to be approved for commercial use by the U.S. Food and Drug Administration. After reading this article, the nuclear medicine technologist should be able to understand the incidence and prevalence of NHL, describe the ibritumomab tiuxetan therapy protocol, explain specific infusion techniques for this protocol, list acquisition parameters after injection of (111)In-ibritumomab tiuxetan, and describe specific safety techniques to keep risk as low as reasonably achievable while performing the therapy protocol.     

90Y-ibritumomab therapy in refractory non-Hodgkin's lymphoma: observations from 111In-ibritumomab pretreatment imaging

Radioimmunotherapy is an effective treatment for non-Hodgkin's lymphoma (NHL). 90Y-ibritumomab is an antibody targeting CD20 receptors on the surface of lymphocytes. We present observations from our clinical experience with 90Y-ibritumomab in the management of NHL. METHODS: This was a retrospective study of 28 NHL patients treated with 90Y-ibritumomab. There were 21 men and 7 women, 36-85 y old. A diagnostic dose of 111In-ibritumomab was administered on day 0, and imaging followed immediately and at 24, 48, and 72 h. The doses of 90Y-ibritumomab ranged from 629 to 1,258 MBq (17-34 mCi). Outcomes were compared with the findings of the 111In-ibritumomab scans. RESULTS: 90Y-ibritumomab induced objective responses in 22 of 28 patients. A complete response was noted in 9 patients, a partial response in 9 patients, and a mixed response in 4 patients. Three patients had stable disease, and 3 patients had disease progression. 111In-ibritumomab findings were positive in 19 patients and negative in 9 patients. A complete response was noted in 2 of 19 patients with positive findings and 7 of 9 with negative findings. A partial response was seen in 7 of 19 patients with positive findings and 1 of 9 with negative findings. Disease progression was observed in 3 of 19 patients with positive findings and 0 of 9 with negative findings. The remaining patients had a mixed response or no changes. CONCLUSION: A higher rate of complete response after 90Y-ibritumomab treatment was seen in patients with negative 111In-ibritumomab findings, whereas a higher rate of disease progression despite therapy was noted in patients with positive 111In-ibritumomab findings. This observation suggests that patients with bulky disease may require more aggressive management.