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Bexxar^®: Novel Radioimmunotherapy for the Treatment of Low-Grade and Transformed Low-Grade Non-Hodgkin’s Lymphoma

Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA

Correspondence: Julie M. Vose, M.D., Department of Internal Medicine, University of Nebraska Medical Center, 987680 Nebraska Medical Center, Omaha, Nebraska, 68198-7680, USA. Telephone: 402-559-3848; Fax: 402-559-6520; e-mail: jmvose{at}unmc.edu

	LEARNING OBJECTIVES

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After completing this course, the reader will be able to:

1. Describe advances in clinical radioimmunotherapy.
   
2. Discuss ongoing translational research in radioimmunotherapy.
   
3. Identify future directions for radioimmunotherapy in cancer medicine.
   

	ABSTRACT

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Purpose. Immunotherapy using monoclonal antibodies to specifically target B cells has provided new hope to many patients with indolent lymphomas, particularly those with chemotherapy-refractory disease. Lymphomas are extremely sensitive to radiation, and significant progress has been made over the last decade in the development of radioimmunotherapy with anti-CD20 antibodies.

Materials and Methods. Herein we review clinical experience with tositumomab and iodine I 131 tositumomab (Bexxar^®; Corixa Corporation; South San Francisco, CA; and GlaxoSmithKline; Philadelphia, PA) in patients with non-Hodgkin’s lymphoma.

Results. Therapy with Bexxar has demonstrated high response rates and long durations of response compared with unconjugated anti-CD20 antibodies in patients with relapsed low-grade and transformed low-grade non-Hodgkin’s lymphomas. Iodine-131 (I-131) has a long history of clinical experience, an excellent safety record, and favorable nuclear and pharmacologic properties. Importantly, the gamma emissions of iodine-131 facilitate accurate dosimetry to calculate the appropriate patient-specific therapeutic activity to deliver a predetermined total-body dose of radiation, thereby minimizing hematologic toxicity. In clinical trials of Bexxar, objective response rates ranged from 54%–71% in heavily pretreated patients. In the pivotal trial, the number of patients with a longer duration of response after treatment with Bexxar was significantly greater than the number of patients with a longer duration of response after their last qualifying chemotherapy regimen. In 76 newly diagnosed patients, the objective response rate was 97%, and 63% of patients achieved complete responses.

Conclusion. These data suggest that Bexxar will become an important new option in the treatment of indolent lymphoma.

Key Words. Radioimmunotherapy • Immunotherapy • Tositumomab • Non-Hodgkin’s lymphoma • Rituximab-refractory

	INTRODUCTION

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Recent developments in the use of monoclonal antibodies to target malignant B cells have produced promising results in the treatment of low-grade (i.e., indolent) non-Hodgkin’s lymphoma (NHL). Investigators have taken advantage of the well-defined surface antigens on differentiated B cells, including CD20 [1], CD19 [2], CD22 [3], CD52 [4], and HLA-DR [5, 6], and have targeted these antigens with a variety of monoclonal antibodies. CD20 is an excellent target for immunotherapy because it is not shed from the cell surface or internalized when bound by antibody, and it is expressed by nearly all B-cell tumors. When anti-CD20 antibodies bind to surface antigens, they induce apoptosis, antibody-dependent cellular cytotoxicity, and complement-dependent cellular cytotoxicity of lymphoma cells [7–10]. Early studies with the chimeric anti-CD20 monoclonal antibody rituximab produced favorable results in patients with relapsed, low-grade NHL. In the pivotal rituximab trial with 166 patients, rituximab induced a 48% objective response (OR) rate, including a 6% complete response (CR) rate, and the median time to progression for responders was 13 months [1]. Although that study established the efficacy of monoclonal antibody therapy in relapsed patients, the low CR rate suggested that there was need for other therapeutic advances. Therefore, studies combining chemotherapy with rituximab or utilizing radioimmunotherapy (RIT) with radionuclide-conjugated monoclonal antibodies have been pursued. The combination of rituximab with conventional CHOP chemotherapy has demonstrated both safety and efficacy in patients with untreated or relapsed low-grade NHL [11]. Recently, RIT has been investigated and has demonstrated higher response rates than those achieved with unconjugated antibodies [1, 12–15].

A variety of radioimmunoconjugates has been investigated in patients with low-grade lymphoma [16], including tositumomab and iodine I 131 tositumomab (Bexxar^®; Corixa Corporation; South San Francisco, CA; http://www.corixa.com; and GlaxoSmithKline; Philadelphia, PA; http://us.gsk.com) and yttrium-90 (Y-90)-labeled Y2B8 (ibritumomab tiuxetan, Zevalin^®; IDEC Pharmaceuticals Corporation; San Diego, CA; http://www.biogenidec.com). The safety and efficacy of therapy with Bexxar were first established in the initial phase I/II study conducted at the University of Michigan, which demonstrated ORs in 71% of patients with relapsed low-grade and transformed low-grade NHL, including CRs in 34% of patients [14]. The efficacy of Bexxar was subsequently confirmed in two multicenter trials in relapsed and refractory patient populations and in a single-center study in newly diagnosed patients. The efficacy and safety of Bexxar in patients with low-grade and transformed low-grade NHL are reviewed based on the cumulative clinical experience over the past 10 years.

	PHARMACOLOGY

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Mechanism of Action
Radioimmunotherapy is a particularly attractive approach for the treatment of NHL for a variety of reasons. First, lymphomas are among the most radiosensitive of all malignancies [17, 18]. Second, unlike total body irradiation, RIT deposits the greatest energy within the tumor, thereby limiting damage to normal tissues. Third, radiolabeled anti-CD20 antibodies have multiple mechanisms of action. In addition to inducing apoptosis and mediating antibody-dependent cellular cytotoxicity and complement-dependent cellular cytotoxicity, radiolabeled antibodies deliver cytotoxic ionizing radiation. Therefore, unlike unconjugated antibodies, radioimmunoconjugates can be effective when the host immune system is not fully functional, can destroy antigen-negative cells within tumors, and can overcome poor penetration of the antibody into tumors. The high-energy beta particles emitted by I-131 are cytotoxic over distances of approximately 1–2 mm (the average path length is 0.8 mm and the maximum path length is 2.4 mm) [19, 20], thus permitting eradication of antigen-negative tumor cells by crossfire from neighboring antibody-coated cells (Fig. 1) [20].

View larger version (35K): [in this window] [in a new window]   Figure 1. Radioisotope crossfire. Illustration of high-energy beta particle emissions from I-131- and Y-90-conjugated antibodies traversing several cell diameters and destroying cells that are inaccessible to the antibody. Adapted with permission from Press et al. [20].

Y-90-labeled anti-CD20 antibodies have also been used in the treatment of lymphoma. Compared with I-131, Y-90 has a shorter half-life and emits higher energy beta particles with a longer average path length. Other beta-emitting isotopes such as copper-67 (Cu-67) appear promising [25], but their availability is extremely limited. Therefore, in terms of half-life, path length, imaging capabilities, and clinical utility, I-131 may have some advantages over other isotopes.

Detailed dosimetry studies conducted at the University of Michigan have also shown that iodine I 131 tositumomab is associated with a favorable tumor-to-normal-organ ratio (Fig. 2). The dose-limiting toxicity of Bexxar therapy, as for all RIT, is hematologic; therefore, the ratio of the absorbed radiation dose to bone marrow versus tumor is critical for determining the therapeutic index. In several phase I and II studies with Bexxar, the absorbed radiation dose to the bone marrow was approximately tenfold lower than the dose to the tumor (Fig. 2). A phase I dose-escalation study determined the maximum tolerated total-body dose (TBD) to be 75 cGy in patients with platelet counts 150,000/mm³ [26]. At this dose level, the absorbed dose to bone marrow was approximately 100 cGy. The majority of patients treated with 75 cGy had only mild-to-moderate myelosuppression 4–6 weeks after treatment, whereas two of three patients treated with whole-body doses of 85 cGy experienced grades 3 and 4 leukopenia and thrombocytopenia [26].

View larger version (12K): [in this window] [in a new window]   Figure 2. Organ versus tumor dosimetry. Organ dosimetry results for three clinical trials with Bexxar therapy are shown. Values are expressed as the mean dose in centigrays (cGy).

View larger version (16K): [in this window] [in a new window]   Figure 3. Efficacy of Bexxar in various patient populations. Overall and complete response rates achieved with Bexxar therapy in different populations of patients with low-grade B-cell NHL. Reprinted with permission from Press [16].

In that trial, 57% of patients had ORs, with a median duration of 9.9 months, and 32% of patients had CRs, with a median duration of 19.9 months [27]. Six patients remained in CR after a median of 50.8 months [29]. The high CR rate and long duration of CR in this trial encouraged further investigation.

Multicenter Pivotal Trial
A multicenter open-label trial was conducted in 60 patients with refractory low-grade or transformed low-grade NHL [12]. The patients were again heavily pretreated, with a median of four (range 2–13) prior chemotherapy regimens, and the median time from diagnosis was 53 months. Moreover, a large proportion of patients (38%) accrued to the study had transformed low-grade NHL. Patients in the trial had received at least two different chemotherapy treatments and had failed to respond to or had relapsed within 6 months after their LQC. Approximately half the patients had received a cyclophosphamide-containing regimen, and 15% had received single-agent fludarabine as their LQC. Following therapy with Bexxar, the OR rate was 65% (intent-to-treat), with a median duration of 6.5 months, and 20% of patients achieved CRs. Using McNemar’s test to compare response rates and the log-rank test to compare response durations (Table 1), it was shown that the response rate and response duration achieved with Bexxar therapy were significantly greater than those achieved with the LQC (28% OR rate, 3% CR rate, and median response duration of 3.4 months) in this cohort.

Bexxar therapy was also associated with a significant improvement in patient-assessed quality of life [30]. Quality-of-life data were collected for 72% of the patients participating in the multicenter pivotal trial at weeks 3, 7, 13, 19, 25, and 38, using the self-administered European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (+3), representing six functional scales and nine symptom scales. By week 19, the mean change from baseline indicated improvements for all scales except insomnia. In general, these improvements continued through week 38 and were comparable with scores reported by the general population. The authors reported statistically significant improvements in emotional and social functions, global health status, nausea and vomiting, and appetite loss at one or more time points. Furthermore, physical, role and social function, and global health status scores showed a >10-point mean change from baseline at week 38.

Treatment of Rituximab Failures
Therapy with Bexxar also has demonstrated safety and efficacy in patients who either failed to respond to rituximab or relapsed following treatment with rituximab. In a cohort of 40 patients with low-grade or transformed low-grade lymphoma, including 24 patients who failed to respond to rituximab, Bexxar therapy produced confirmed ORs in 68% of patients, with a median response duration of 14.7 months [31]. Moreover, 30% of patients had CRs, and the median duration of CR had not been reached.

Multicenter Expanded-Access Study
The efficacy of Bexxar therapy was further supported by a multicenter expanded-access study involving 65 academic and community sites in which the interim efficacy of Bexxar therapy in 475 patients with relapsed or refractory NHL enrolled in the study was recently assessed [28]. Of the 394 patients evaluable for response, 59% had ORs, with a median duration of 15 months, and 26% had CRs, with a median duration not reached after 9 months. The median time to progression for responders was 18 months.

Treatment of Transformed Low-Grade NHL
Transformation of low-grade lymphoma to a more aggressive histology is associated with poor survival (10-year survival rate of 13%) despite currently available treatment [32]. Therefore, the efficacy of Bexxar in transformed low-grade NHL is of particular interest. Data are available from 71 evaluable patients with transformed low-grade NHL who were treated with Bexxar in five trials [33]. That analysis included any patient with a biopsy consistent with histologic transformation at any time during the course of their disease and prior to study entry. For patients included in this analysis, the median time from diagnosis was 74 months (range 8–334 months), the median time from transformation was 21 months (range 0–123 months), and the median number of prior therapies was four (range 1–11). In addition, 28% of the patients had bulky disease and 57% had elevated lactate dehydrogenase (LDH) levels. Treatment with Bexxar resulted in an OR rate of 39%, with a median response duration of 20 months. In addition, 25% of patients had CRs, with a median duration of 36.5 months [33]. Based on these data, therapy with Bexxar appears to be effective in the treatment of transformed low-grade NHL and produces durable responses in this patient population. However, the transformed patients treated in this trial had a long duration between transformation and therapy with Bexxar and, therefore, the results may not be typical in all transformed NHL patients.

Treatment of Patients with Poor Prognostic Features
The efficacy of Bexxar therapy has also been evaluated in patients with poor prognostic factors, including elderly patients and patients with bulky disease. In a retrospective analysis, data were collected for 70 patients >60 years of age (median 69 years, range 61–82 years) with low-grade (60%) or transformed low-grade (34%) NHL treated in phase I-III trials from 1990–1999 [34]. In this cohort, 31% patients had bulky disease (>500 g). Treatment with Bexxar resulted in ORs in 60% of patients, with a median duration of 9 months, and 20% of patients had CRs, with a median duration not reached after a median of 15 months follow-up. A similar analysis of phase I-III clinical trials showed that therapy with Bexxar is efficacious in patients with a number of poor prognostic factors, including age >60 years, bulky disease, elevated LDH levels, and four or more prior chemotherapies (Table 2) [35].

Durability of Responses
An analysis of the duration of responses to Bexxar therapy has demonstrated the excellent durability of CRs in 269 evaluable patients with low-grade or transformed low-grade NHL treated with Bexxar from 1990–1999, who have been followed for a median of 1.5 years [38]. Within this population, 88 patients (33%) had CRs and 74 patients (28%) had confirmed CRs (i.e., two or more assessments 4 weeks apart). The median CR duration was 3.25 years; the median confirmed CR duration was 5 years. The median response duration had not been reached in newly diagnosed patients, and previously treated patients had median CR durations ranging from 20–40 months.

Safety
Radioimmunotherapy with Bexxar in patients with low-grade and transformed low-grade NHL was shown to be safe and effective in five separate clinical trials and in a multicenter expanded-access study [14, 27, 28, 39–44]. All these trials used dosimetry to determine the patient-specific therapeutic dose required to administer the maximum tolerated TBD (75 cGy). Administration of a patient-specific therapeutic dose allows for greater uniformity of tumor dose with more predictable hematologic toxicities. This is critically important because total body residence times for the radiolabeled antibody can vary depending on tumor burden, bone marrow involvement, and the presence of splenomegaly. In all of these trials, therapy with Bexxar was well tolerated and hematologic toxicities were acceptable.

As with the infusion of any foreign protein, treatment with Bexxar can be associated with infusion-related adverse events. The most common nonhematologic adverse events associated with Bexxar therapy are shown in Table 3 [43] and were typically mild to moderate in severity. In the multicenter, phase II trial, Bexxar infusions were well tolerated: 83% of patients had no infusion reactions, and there were no grade 3 infusion reactions reported [27]. Only 4% of infusions required a rate adjustment. In comparison, 33% of patients treated with rituximab required dose interruptions during the first infusion [1].

Hematologic and nonhematologic secondary malignancies are of concern with any radiation-based therapy. To date, at a median follow-up of 1.5 years (range 0–8.2 years) from the dosimetric dose, secondary myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) has been reported in 19 (3.1%) of 620 heavily pretreated patients who received therapy with Bexxar [47]. Those patients had received a median of three prior therapies, and the median time from diagnosis to study entry was 45 months. This observed incidence of secondary MDS/AML following Bexxar therapy is consistent with the reported cumulative incidence in lymphoma patients 5–6 years after initial cytotoxic therapy [48]. A retrospective review of baseline bone marrow biopsies showed that five of those patients had evidence of MDS/AML at study entry, and chromosomal analysis at clinical diagnosis of MDS/AML revealed changes in chromosomes 5 and/or 7 consistent with alkylator-induced chromosomal damage in 11 of 12 patients tested. Moreover, none of the 76 newly diagnosed patients who were treated with Bexxar had developed MDS/AML at a median follow-up of 4.1 years (range 0.7–6.3 years) [47]. While longer follow-up is needed to determine the potential contribution of treatment with Bexxar to the development of MDS/AML, none of the available data from multiple studies demonstrate that therapy with Bexxar substantially increased the risk above what would be expected in a group of heavily pretreated lymphoma patients.

Dosing and Administration
The complete course of therapy with Bexxar is carried out in two phases. First, patients receive a trace-labeled dosimetric dose, and dosimetry studies are conducted to establish the patient-specific therapeutic dose. Second, a single therapeutic dose is administered. With appropriate instructions, the patient can generally be treated on an outpatient basis.

Patient-Specific Dosing
The administered dose of Bexxar is calculated based on patient-specific variables. Dosimetry ensures that each patient receives the maximum tolerated TBD, which should maximize therapeutic benefit and ensure that organ toxicity is minimal. The delivered therapeutic dose is determined based on the clearance rate of the radiolabeled antibody from each individual patient (i.e., patient-specific residence time), which is affected primarily by the patient’s lean body mass and tumor burden [49]. Patients first receive an infusion of unlabeled antibody followed by a trace-labeled dosimetric dose of antibody, and total-body gamma camera counts are then obtained at three times over the next 6–7 days. The therapeutic dose is then calculated based on the effective half-life of the antibody to ensure that the patient receives a dose calculated to deliver a 75-cGy TBD (for patients with baseline platelet counts 150,000/mm³). Patients who have platelet counts of 100,000–149,999/mm³ receive TBDs of 65 cGy; Bexxar therapy is not recommended for patients with platelet counts below 100,000/mm³. The actual amount of radioactivity administered to each patient is variable (ranging from 45–239 mCi), with a median of 81.8 mCi [45].

Details of the Bexxar regimen are illustrated in Figure 4 [50]. Oral iodine supplements to block I-131 uptake by the thyroid gland are administered beginning 1 day before administering the dosimetric infusion and continuing for 2 weeks after the therapeutic dose. Patients are also pretreated with oral acetaminophen (650 mg) and either diphenhydramine (50 mg) or chlorpheniramine (4 mg) 1 hour before each infusion of tositumomab to reduce infusion reactions to the antibody. A 60-minute infusion of 450 mg unlabeled (i.e., cold) tositumomab is administered before administering the dosimetric dose on day 0 to improve biodistribution of the radiolabeled antibody. The dosimetric dose of iodine I 131-labeled tositumomab (5 mCi) is then administered via a 20-minute infusion followed by a 10-minute flush. The patient then undergoes three whole-body gamma camera counts (immediately postinfusion on day 0; on day 2, 3, or 4; and on day 6 or 7). Based on the calculated residence time of the antibody, a patient-specific therapeutic dose is calculated. From days 7–14, the patient receives a 60-minute infusion of 450 mg cold tositumomab followed by the therapeutic dose of iodine I 131 tositumomab via a 20-minute infusion plus a 10-minute flush. Dosage adjustments are made for patients with low platelet counts (100,000–149,999/mm³) and for obese patients (>135% of ideal body weight).

View larger version (25K): [in this window] [in a new window]   Figure 4. Treatment regimen for therapy with Bexxar. X = patient-specific dose. Reprinted with permission from Hohenstein et al. [50].

• The hematologist/oncologist is responsible for identifying appropriate patients for treatment with Bexxar (i.e., patients with relapsed or refractory low-grade or transformed low-grade B-cell NHL), prescribing the SSKI supplement, monitoring the patient while in the hospital and performing the follow-up to determine response to treatment, and managing adverse events.
  
• The nuclear medicine physician or radiation oncologist is primarily responsible for prescribing and directly supervising the administration of Bexxar and overseeing the calculations to determine the patient-specific therapeutic dose. After administering the therapeutic dose, the nuclear medicine physician, radiation safety officer, or radiation oncologist is responsible for determining whether the patient can be released and for providing the patient with necessary radiation safety precautions.
  
• The nuclear pharmacist, who is onsite at the UNMC, is responsible for ordering, preparing, and administering both the cold Bexxar infusions.
  
• The nuclear medicine technologist is responsible for performing whole-body gamma camera scans and ensuring the accuracy of the dosimetric data used to calculate the therapeutic dose.
  
• The oncology nurse assists the nuclear pharmacist, monitors the patient during infusions, and treats any infusion-related reactions.
  
• The oncology or radiology nurse coordinator has the primary responsibility for initial patient screening, ordering pharmaceuticals, and scheduling treatment, including gamma camera scans. The nurse coordinator is also responsible for patient education.
  
• The radiation safety officer is responsible for monitoring all iodine I 131 tositumomab infusions for safety and patient radiation levels during and after treatment.
  

General Radiation Safety
Bexxar can be safely administered in an outpatient oncology clinic, although patients are required to have access to a nuclear medicine facility equipped to perform standard whole-body gamma camera counts. The radiation safety precautions followed during the administration of Bexxar are similar to those followed during standard radioiodine therapy; however, because the I-131 is conjugated to an antibody, the problems associated with the volatility of sodium iodide are minimized. It is recommended that the infusion equipment be dedicated exclusively to administering Bexxar; however, under normal operating conditions, infusion pumps should not become contaminated. During the infusion, the iodine I 131 tositumomab is shielded, patients are usually isolated in a specially prepared room, and access to the room is restricted. Patients can generally be released immediately after the infusion, as described below.

Patient Release Guidelines
The release of patients administered Bexxar must be carried out in compliance with federal and state regulations. In states that have adopted the Nuclear Regulatory Commission (NRC) regulations, patient release is carried out in compliance with NRC regulations specified in the Code of Federal Regulations 10 CFR Part 35 and Regulatory Guide 8.39, Release of Patients Administered Radioactive Materials [52]. This regulatory guide provides specific guidelines that must be followed for determining when a patient can be released from the hospital. These new regulations specify that patients can be released as long as the radiation doses to other individuals (e.g., family members) are not likely to exceed 500 millirems (mrem).

Determining Patient-Specific Release Criteria
Patient-specific release criteria that are consistent with federal regulations have been developed based on the total body residence time of the antibody (which is determined by serial gamma camera scans after administering the dosimetric dose) and the measured dose rate at 1 m in mrem/hour (measured immediately after administering the therapeutic dose). With this information, a simple look-up table is consulted to determine if the patient can be released. Most patients can be released immediately after administering the therapeutic dose.

A recent study estimated the radiation exposure of family members based on an analysis of 139 patients treated with Bexxar [53]. The mean activity administered to these patients was 84 mCi (range 33–161 mCi), and the mean observed dose rate at 1 m was 10.9 mrem/hour (range 4–24 mrem/hour). The estimated radiation exposure to maximally exposed family members and caregivers ranged from 195–496 mrem. This study suggested that all 139 patients qualified for immediate release after Bexxar therapy.

Patient-Release Instructions
Once it has been determined that a patient can be released, NRC regulations state that the patient must be provided with clear, written instructions. An example of such patient instructions is shown in Figure 5 [54]. These instructions advise patients on how close they can be to others and how they should conduct themselves and dispose of bodily wastes to minimize radiation exposure to others. For example, patients are instructed to sleep in a separate bed (6 feet from others), not to take a long trip (4 hours) during which they will be sitting near others, to maintain a safe distance (6 feet) from others, and to avoid contact with children and pregnant women. The duration of these restrictions is calculated on each individual patient’s residence time and dose rate at 1 m. For example, a patient with a residence time of 75 hours and a dose rate of 10 mrem/hour would be restricted to sleeping in a separate bed for 6 days, not taking long trips for 1 day, and maintaining safe distances from children and pregnant women for 9 days. When a patient has demonstrated an understanding of these restrictions and appears capable of complying based on an interview, that patient can be released.

View larger version (32K): [in this window] [in a new window]   Figure 5. Instructions for releasing a patient treated with Bexxar [54].

	CONCLUSIONS

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Radioimmunotherapy with Bexxar has been shown to be safe and effective for the treatment of indolent lymphoma. The advantage of Bexxar over conventional radiotherapy, chemotherapy, and unconjugated antibodies is the ability to target a patient-specific dose of radiation to the tumor with minimal toxicity to normal organs. Clinical trials have demonstrated that treatment with Bexxar induces high overall and CR rates and durable complete remissions in relapsed and refractory patients, newly diagnosed patients, and patients who failed rituximab. In relapsed and refractory patients, Bexxar produced superior response rates and durations when compared with patients’ LQC and improved quality of life, thus providing a viable treatment option for patients who have become refractory to chemotherapy. Hematologic toxicities were generally short term, predictable, and manageable. It has also been demonstrated that Bexxar can be administered safely in the outpatient setting by following established and validated guidelines.

	FUTURE DIRECTIONS

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Given the proven efficacy of therapy with Bexxar in patients with relapsed and refractory low-grade NHL, it may play an important role as second-line therapy in patients who have failed prior chemotherapy, rituximab, or both. High response rates and durable responses have also been demonstrated in patients with transformed low-grade NHL, suggesting that Bexxar could potentially be effective in the treatment of aggressive lymphoma. Its role as first-line therapy for indolent lymphoma has yet to be defined. However, several cooperative group trials are investigating therapy with Bexxar in combination with chemotherapy in newly diagnosed patients. Based on the encouraging results of the SWOG trial S9911, an intergroup trial has been initiated to compare CHOP plus rituximab with CHOP plus Bexxar for follicular lymphoma. A myeloablative I-131-tositumomab regimen with stem-cell support is also being actively investigated and appears promising. In this setting, RIT has advantages over total-body irradiation and is less toxic than many preparative chemotherapy regimens. The role of RIT for the treatment of indolent lymphoma will undoubtedly continue to evolve.

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Top Learning Objectives Abstract Introduction Pharmacology Conclusions Future Directions References

 

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