Yttrium 90 (90Y) ibritumomab tiuxetan (Zevalin), a radiolabeled monoclonal antibody against the CD20 antigen, is indicated for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL), including patients with rituximab-refractory follicular NHL. Data on 211 patients treated in four clinical trials were analysed to compare the efficacy and safety of 90Y ibritumomab tiuxetan when it was used after the first relapse of NHL and when it was used after two or more prior therapies. Sixty-three patients (30%) were treated with 90Y ibritumomab tiuxetan after their first relapse and 148 (70%) after two or more prior therapies. Demographics, disease characteristics and the frequency of adverse events were similar in all groups, with the exception of a higher rate of marrow involvement in first-relapse patients than in patients with two or more prior therapies (57% vs. 39%; P < 0.05). The complete response rate [confirmed (CR) and unconfirmed (Cru)] was higher in first-relapse patients (49% vs. 28%; P < 0.01), and the median time to progression (TTP) was longer (12.6 vs. 7.9 months; P < 0.05). In patients with follicular NHL, the differences were even more pronounced (CR/CRu: 51% vs. 28%; P < 0.01; TTP: 15.4 vs. 9.2 months; P < 0.05). 90Y ibritumomab tiuxetan has substantial clinical benefits as a second-line therapy, especially in patients with follicular NHL. The quality of disease remissions obtained when 90Y ibritumomab tiuxetan is administered after first relapse appears to be comparable with that observed with most chemotherapy regimens in first-relapse patients.

We report the case of a 15-yr-old girl who developed secondary acute myelogenous leukemia (AML) 4 yr after completion of therapy for metastatic Ewing sarcoma (primary right acetabulum with metastatic disease to the lungs). Peripheral blood stem cells were collected after the second cycle of chemotherapy with the plan for future consolidation with high-dose chemotherapy and autologous stem cell rescue; however, because of the patient's excellent response to chemotherapy and surgery, therapy was completed without the need for high-dose chemotherapy. No human leukocyte antigen (HLA)-matched related donor was available for a bone marrow transplant. Because of previous lung radiation, high-dose samarium [30 mCi/kg of samarium-153 ethylenediaminetetramethylenephosphonate (Sm-153-EDTMP) day -14] and melphalan (140 mg/m(2) day -2) were chosen as the conditioning regimen to avoid potential lung complications. The patient received an infusion of 6.1 x 10(8)/kg mononuclear autologous cells on day 0. She achieved engraftment on day +23. Three years after transplantation, she continues to have complete remission. Samarium and melphalan constitute a well-tolerated regimen with potential antileukemic activity.

8534 Background: Osteoblastic metastases can avidly concentrate bone-seeking radiopharmaceuticals. We sought to increase effectiveness of high-dose 153Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP; Quadramet) on osteosarcomas using a radiosensitizer, gemcitabine. Methods: Fourteen patients with osteoblastic lesions of osteosarcoma were treated. With high-dose 153Sm-EDTMP (30 mCi/kg) and stem cell support. Gemcitabine was administered 1 day after samarium. Imaging studies used to assess response. Results: The residual total body radioactivity was within the safe range of <3.6 mCi on day +14 (1.1 +/− 0.4 mCi; range 0.67–1.8 mCi). Expected cytopenias from skeletal binding of the radiopharmaceutical occurred within 14 days. Peripheral blood progenitor cells (PBPC) were infused 2 weeks after samarium in 11 patients; three patients had marrow infused. Blood count recovery was uneventful after PBPC in 11/11 patients. Toxicity from the daily gemcitabine regimen (250 mg/M2/day x 5) was excessive (grade 3 mucositis; N=1). Toxicity from a single infusion of gemcitabine (1500 mg/M2) in combination with 153Sm-EDTMP was minimal (pancytopenia). There were no reported episodes of hemorrhagic cystitis (hematuria) or nephrotoxicity. At the 6–8 week follow-up there were 6 PR, 2 mixed responses, and 6 patients with progressive disease. In the 12 patients followed >1 year, there have been no durable responses. Conclusions: High-dose 153Sm-EDTMP + gemcitabine has activity in osteoblastic osteosarcoma lesions, but recurrence is very common. Other strategies such as repeated standard doses of samarium with gemcitabine and/or use of additional measures of local and systemic control should be considered for more prolonged control of osteoblastic metastases. No significant financial relationships to disclose.

AIM:Yttrium-90 ((90)Y) ibritumomab tiuxetan (Zevalin) radioimmunotherapy is an effective treatment for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL), with overall response rates ranging from 74% to 82%. This retrospective analysis was conducted to determine the number of patients achieving long-term durable responses with (90)Y ibritumomab tiuxetan treatment.MATERIALS AND METHODS:The medical records of patients (n = 211) with relapsed, refractory, or transformed indolent CD20+ B-cell NHL who were treated with 90Y ibritumomab tiuxetan were reviewed. Time to progression (TTP) of > or =12 months was noted in 78 patients (37%), who were identified as long-term responders and were further characterized.RESULTS:Median age of the long-term responders was 58 years (range, 24-80 years) with 44% over 60 years, and 55% were male. Notably, 59% of patients had received > or =2 prior regimens, 33% had received > or =3 prior regimens, and 37% had failed to respond to immediate prior therapy. Median response duration was 28.1 months (range, 10.5-80.3+ months). Median TTP was 29.3 months (range, 12.1-81.5+ months). In patients with ongoing response, median TTP was 53.9 months (range, 49-82+ months).CONCLUSIONS:(90)Y ibritumomab tiuxetan produces durable long-term responses in patients with relapsed/refractory B-cell NHL. Failure to respond to prior therapy does not preclude achieving a long-term response with 90Y ibritumomab tiuxetan.

Osteoblastic metastases and osteosarcoma can avidly concentrate bone-seeking radiopharmaceuticals. We sought to increase effectiveness of high-dose (153)Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP, Quadramet) on osteosarcomas using a radiosensitizer, gemcitabine. Fourteen patients with osteoblastic lesions were treated with 30 mCi/kg 153Sm-EDTMP. Gemcitabine was administered 1 day after samarium infusion. Residual total body radioactivity was within the safe range of <3.6 mCi on day +14 (1.1 +/- 0.4 mCi; range, 0.67-1.8 mCi). All patients received autologous stem cell reinfusion 2 weeks after 153Sm to correct expected grade 4 hematopoietic toxicity. Peripheral blood progenitor cells were infused in 11 patients; three patients had marrow infused. Blood count recovery was uneventful after peripheral blood progenitor cells in 11 of 11 patients. Toxicity from a single infusion of gemcitabine (1,500 mg/m2) in combination with 153Sm-EDTMP was minimal (pancytopenia). However, toxicity from a daily gemcitabine regimen (250 mg/m2/d x 4-5 days) was excessive (grade 3 mucositis) in one of two patients. There were no reported episodes of hemorrhagic cystitis (hematuria) or nephrotoxicity. At the 6- to 8-week follow-up, there were six partial remissions, two mixed responses, and six patients with progressive disease. In the 12 patients followed >1 year, there have been no durable responses. Thus, although high-dose 153Sm-EDTMP + gemcitabine has moderate palliative activity (improved pain; radiologic responses) in this poor-risk population, additional measures of local and systemic control are required for durable control of relapsed osteosarcoma with osteoblastic lesions. The strategy of radioactive drug binding to a target followed by a radiosensitizer may provide synergy and improved response rate.

6574 Background: Updated time to disease progression (TTP) and duration of response (DR) are reported for responders from a multicenter phase I/II dose-escalation trial of 90Y ibritumomab tiuxetan (Zevalin®) in 51 patients (pts) with relapsed or refractory CD20+ B-cell NHL. Methods: 5 pts were treated at a dose of 0.2 mCi/kg, 15 at 0.3 mCi/kg, and 30 at 0.4 mCi/kg; 1 pt was not treated. Maximum tolerated dose (MTD) was 0.4 mCi/kg for pts with baseline platelets (plts) ≥ 150,000/μL (0.3 mCi/kg for plts 100,000–149,000/μL). Maximum dose for all pts was 32 mCi. Median age was 60 years (yrs) (range, 24–82). Median time from diagnosis to treatment was 3.8 yrs (range, 0.7–33.1). Median number of prior chemotherapy regimens was 2 (range, 1–7); 47 pts (92%) had received an anthracycline. 10 pts (20%) were resistant to prior chemotherapy. At study entry, 59% of pts had ≥ 1 tumor mass ≥ 5 cm; 43% had bone marrow involvement. Results: TTP and DR in responders were updated, response rates (RR) reported at all dose levels by International Workshop Response Criteria. Complete response (CR), CR unconfirmed (CRu), and partial response (PR) rates were 29%, 22%, and 22%, respectively, for an overall RR (ORR) of 73% (51% CR/CRu). ORR in pts with follicular lymphoma (FL) was 85% (58% CR/CRu, 27% PR). TTP and DR in all responders were 12.6 months (mos) and 11.7 mos, respectively. At MTD, TTP and DR in complete responders (CR/CRu) were 28.3 and 27.5 mos, respectively. 9 pts (24% of responders) had TTP >3 yrs; 5 had FL and 4 had diffuse large cell lymphoma (DLCL). 5 pts (FL, 3; DLCL, 2) are still in CR (range, 60+-74+ mos). Conclusions: 90Y ibritumomab tiuxetan produces high RRs and durable responses in pts with relapsed or refractory B-cell NHL. Durable responses >5 years have been seen in FL and DLCL. Because most relapses in DLCL occur early, the 2 DLCL pts with durable remissions might be cured. This observation provides the basis for further studies to define the efficacy of 90Y ibritumomab tiuxetan in relapsed DLCL. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biogen/IDEC Biogen/IDEC Biogen/IDEC Biogen/IDEC

Ibritumomab tiuxetan is an ant-CD20 murine IgG1 K monoclonal antibody (ibritumomab) conjugated to the linker-chelator tiuxetan, which securely chelates In-111 for imaging or dosimetry and Y-90 for radioimmunotherapy (RIT). Dosimetry and pharmacokinetic data from 4 clinical trials of Y-90-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 17 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 greater than or equal to100,000 cells/mm(3) for the reduced Y-90-ibritumomab tiuxetan administered dose (7.4-11 MBq/kg [0.2-0.3 mCi/kg]) or greater than or equal to150,000 cells/mm3 for the standard Y-90-ibritumomab tiuxetan administered dose (15 MBq/kg [0.4 mCi/kg]). Patients were given a tracer administered dose of 185 MBq (5 mCi) In-111-ibritumomab tiuxetan on day 0, evaluated with dosimetry, and then a therapeutic administered dos of 7.4-15 MBq/kg (0.20.4 mCi/kg) Y-90-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 Y-90 in blood and major organs were estimated from In-111 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 Y-90 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 Y-90-ibritumomab tiuxetan RIT on the basis of a fixed, weight-adjusted dosing schedule. Dosimetry and pharmacokinetic results do not correlate with toxicity.

This was a 30-patient Phase II trial of reduced-dose (90)Y ibritumomab tiuxetan (Zevalin) RIT for patients with low-grade, follicular, or transformed B-cell NHL and mild thrombocytopenia. Patients were given an imaging dose of (111)In-labeled ibritumomab tiuxetan for dosimetry measurements. One week later, patients were administered a therapeutic dose of 0.3 mCi/kg (11 MBq/kg) (90)Y ibritumomab tiuxetan. Both (111)In- and (90)Y-labeled ibritumomab tiuxetan doses were preceded by an infusion of 250 mg/m(2) rituximab (Rituxan, MabThera) an unlabeled chimeric anti-CD20 antibody, to clear peripheral blood B cells and improve biodistribution of the radiolabeled antibody. For all 30 patients, normal organ and red marrow radiation absorbed doses were well below protocol-defined limits of 2000 cGy and 300 cGy, respectively. Median radiation absorbed doses were 48 cGy to red marrow (range: 6.5-95 cGy), 393 cGy to liver (range: 92-1581 cGy), 522 cGy to spleen (range: 165-1711 cGy), 162 cGy to lungs (41-295 cGy), and 14 cGy to kidneys (0.03-65 cGy). Though most correlative analyses were negative, certain analyses demonstrated a statistically significant correlation between the severity or duration of thrombocytopenia and pharmacokinetic or dosimetric parameters. These correlations were not consistent across the total patient population, and therefore, could not be exploited to predict hematologic toxicity.

Zevalin (ibritumomab tiuxetan) radioimmunotherapy is a novel treatment for non-Hodgkin's lymphoma (NHL). The Zevalin regimen includes 5 mCi (111)In-labeled Zevalin on Day 1, followed by serial anterior and posterior planar gamma images for imaging or dosimetry. On Day 8, patients receive 0.4 mCi/kg (90)Y Zevalin for radioimmunotherapy. Both Zevalin doses are preceded by 250 mg/m(2) rituximab to clear peripheral B cells and improve biodistribution of the radiolabeled antibody. In a 143-patient, Phase III, randomized study, the Zevalin regimen produced a significantly higher overall response rate than rituximab for relapsed or refractory, low-grade, follicular, or transformed NHL (80% versus 56%, p = 0.02). Fifteen patients from the Zevalin arm of this study were randomly selected for additional radiation dosimetry. (90)Y residence times were calculated from (111)In image analysis data. MIRDOSE3.1 radiation absorbed dose estimates to normal tissues were highest for spleen, testes, and liver, with considerably lower doses reaching heart, lung, intestines, red marrow, and kidneys. Radiation absorbed doses to organs and marrow were within a safe range following administration of 0.4 mCi/kg (90)Y Zevalin.

PURPOSE:Radioimmunotherapy (RIT) with yttrium-90 ((90)Y)-labeled anti-CD20 antibody ((90)Y ibritumomab tiuxetan; Zevalin, IDEC Pharmaceuticals Corporation, San Diego, CA) has a high rate of tumor response in patients with relapsed or refractory, low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL). This study presents the safety data from 349 patients in five studies of outpatient treatment with (90)Y ibritumomab tiuxetan.PATIENTS AND METHODS:Patients received rituximab 250 mg/m(2) on days 1 and 8, and either 0.4 mCi/kg (15 MBq/kg) or 0.3 mCi/kg (11 MBq/kg) of (90)Y ibritumomab tiuxetan on day 8 (maximum dose, 32 mCi). Patients were observed for up to 4 years after therapy or until progressive disease.RESULTS:Infusion-related toxicities were typically grade 1 or 2 and were associated with rituximab. No significant organ toxicity was noted. Toxicity was primarily hematologic, with nadir counts occurring at 7 to 9 weeks and lasting approximately 1 to 4 weeks depending on the method of calculation. After the 0.4-mCi/kg dose, grade 4 neutropenia, thrombocytopenia, and anemia occurred in 30%, 10%, and 3% of patients, respectively, and after the 0.3-mCi/kg dose, these grade 4 toxicities occurred in 35%, 14%, and 8% of patients, respectively. The risk of hematologic toxicity increased with degree of baseline bone marrow involvement with NHL. Seven percent of patients were hospitalized with infection (3% with neutropenia) and 2% had grade 3 or 4 bleeding events. Myelodysplasia or acute myelogenous leukemia was reported in five patients (1%) 8 to 34 months after treatment.CONCLUSION:Single-dose (90)Y ibritumomab tiuxetan RIT has an acceptable safety profile in relapsed NHL patients with less than 25% lymphoma marrow involvement, adequate marrow reserve, platelets greater than 100,000 cells/ micro L, and neutrophils greater than 1,500 cells/ micro L.

Several reports have suggested a benefit from radioactive iodine (RAI) therapy in Tg-positive, whole-body scan-negative patients with follicular cell-derived thyroid cancer, who were said to have high rates of visualization of uptake in metastases after therapeutic doses of RAI. We sought to evaluate the rate of visualization of RAI uptake in these patients and determine the effect of such therapy on tumor progression and Tg levels. We studied 24 consecutive patients who had been treated with high-dose RAI, four of whom had no evidence of metastasis or persistent cancer. Our results showed that four patients had some uptake in posttherapy scans: in the neck, lung, and mediastinal metastases in one patient, in the thyroid remnant in two, and in a possible neck microrecurrence in one. In 13 patients with macrometastases-tumors 1 cm or greater-tumors progressed and serum Tg increased; five have died of thyroid cancer. The disease remained stable in the seven patients with micrometastases. We concluded that in high-risk patients with follicular cell-derived thyroid cancer with high Tg levels and negative diagnostic whole-body scans, only a small number showed meaningful uptake after high doses of RAI. Therefore, widespread use of empiric RAI therapy for such patients who have a large tumor burden should not be encouraged.

The treatment of malignant lymphoma has improved over the past 20 years, but the majority of patients are not cured. New modalities using targeted therapy based on new information in molecular biology and immunology hold promise for better outcomes with less toxicity. We review data on the use of radiolabeled monoclonal antibodies directed against the CD20 antigen on malignant B cells. We discuss the major radionuclides available, iodine 131 (131I), tositumomab, and yttrium 90 (90Y) ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals, San Diego, CA) and present data on new approaches in labeling antibodies that have facilitated their use. Clinical trial data with the yttrium-labeled antibodies are discussed. The use of dosimetry as a means for predicting toxicity is discussed, and the questions of long-term toxicity (late effects) are addressed. These targeted approaches to the treatment of malignancy, and lymphoma in particular, hold great promise. Semin Oncol 29 (suppl 2):87-92. Copyright © 2002 by W.B. Saunders Company.

BACKGROUND. Zevalin consists of a murine anti-CD20 monoclonal antibody (ibritumomab) conjugated to the linker-chelator tiuxetan, which securely chelates indium-111 (In-111) for imaging and dosimetry and yttrium-90 (Y-90) for radioimmunotherapy (RIT). Previous trials involving rituximab-naive patients have demonstrated excellent targeting of Zevalin to CD20+ B-cell non-Hodgkin lymphoma with minimal uptake in normal organs. The purpose of this trial was to perform In-111-Zevalin imaging in patients with rituximab-refractory tumors to determine normal organ dosimetry.METHODS. Twenty-seven patients were given an imaging dose of 5 mCi (185 MBq)In-111-Zevalin on Day 0, evaluated with dosimetry, and then given a therapeutic dose of 0.4 mCi/kg (15 MBq/kg) Y-90-Zevalin on Day 7. Both Zevalin doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B cells and improve Zevalin biodistribution. Residence times for Y-90 in blood and major organs were estimated from In-111 biodistribution, and the MIRDOSE3 computer software program was used to calculate absorbed radiation doses to organs and red marrow.RESULTS. Median estimated absorbed radiation doses from Y-90-Zevalin were 8.1 Gray (Gy) (range, 4.2-23.0 Gy) to the spleen, 5.1 Gy (range, 2.6-12.0 Gy) to the liver, 2.0 Gy (range, 1.4-5.3 Gy) to the lungs, 0.22 Gy (range, < 0.01-0.66 Gy) to the kidneys, and 0.74 Gy (range, 0.29-1.2 Gy) to the red marrow. These results are consistent with those from earlier Zevalin trials in rituximab-naive patients. Hematologic toxicity was manageable and did not correlate with estimates of red marrow or total-body absorbed radiation dose.CONCLUSIONS. Zevalin treatment of rituximab-refractory follicular NHL patients at 0.4 mCi/kg resulted in acceptable estimates of absorbed radiation dose to organs, similar to those observed in other Zevalin-treated populations. Cancer 2002;94: 1349-57. (C) 2002 American Cancer Society.

PURPOSE:Yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin; IDEC Pharmaceutical, San Diego, CA) is an effective therapy for patients with relapsed B-cell non-Hodgkin's lymphoma. The predominant toxicity of 90Y ibritumomab tiuxetan has been myelosuppression, and concern has been expressed about the tolerability of further treatment after this therapy. The goal of this analysis was to evaluate the therapy given to patients who relapsed after 90Y ibritumomab tiuxetan.PATIENTS AND METHODS:A retrospective analysis was performed on 58 patients treated at a single institution on five separate protocols that used 90Y ibritumomab tiuxetan 0.4 mCi/kg. All patients had experienced disease progression after 90Y ibritumomab tiuxetan treatment and received subsequent therapy. The toxicity seen in this cohort of patients with subsequent treatment regimens was analyzed and compared with that of control groups who did not receive 90Y ibritumomab tiuxetan.RESULTS:The median number of subsequent therapies was two (range, one to seven). Sixteen (28%) of the 58 patients received growth factor support with subsequent chemotherapy, and two patients were treated with reduced doses because of persistent pancytopenia. Eight patients subsequently had an autologous stem-cell transplantation with stem cells collected after 90Y ibritumomab tiuxetan therapy. Excluding patients hospitalized at the time of transplantation, 13 patients were hospitalized for neutropenic fever, thrombocytopenia, or both. When compared to patients who did not receive 90Y ibritumomab tiuxetan, there was no significant difference in toxicity.CONCLUSION:We conclude that chemotherapy or autologous stem-cell transplantation after prior therapy with 90Y ibritumomab tiuxetan is feasible and reasonably well tolerated. The toxicity with subsequent therapy seems similar to that in patients not treated with 90Y ibritumomab tiuxetan.

Mildly thrombocytopenic patients with relapsed or refractory low-grade non-Hodgkin lymphoma (NHL) have an increased risk of chemotherapy-induced myelosuppression following treatment. The safety and efficacy of radioimmunotherapy with a reduced dose of (90)Y ibritumomab tiuxetan (0.3 mCi/kg [11 MBq/kg]; maximum 32 mCi [1.2 GBq]) was evaluated in 30 patients with mild thrombocytopenia (100-149 x 10(9) platelets/L) who had advanced, relapsed or refractory, low-grade, follicular, or transformed B-cell NHL. The ibritumomab tiuxetan regimen included an infusion of rituximab (250 mg/m(2)) and injection of (111)In ibritumomab tiuxetan (5 mCi [185 MBq]) for dosimetry evaluation, followed 1 week later with rituximab (250 mg/m(2)) and (90)Y ibritumomab tiuxetan (0.3 mCi/kg [11 MBq/kg]). Patients (median age, 61 years; 90% stage III/IV at study entry; 83% follicular lymphoma; and 67% with bone marrow involvement) had a median of 2 prior therapy regimens (range, 1-9). Estimated radiation-absorbed doses were well below the study-defined maximum allowable for all 30 patients. With the use of the International Workshop criteria for NHL response assessment, the overall response rate was 83% (37% complete response, 6.7% complete response unconfirmed, and 40% partial response). Kaplan-Meier estimated median time to progression (TTP) was 9.4 months (range, 1.7-24.6). In responders, Kaplan-Meier estimated median TTP was 12.6 months (range, 4.9-24.6), with 35% of data censored. Toxicity was primarily hematologic, transient, and reversible. The incidence of grade 4 neutropenia, thrombocytopenia, and anemia was 33%, 13%, and 3%, respectively. Reduced-dose ibritumomab tiuxetan is safe and well tolerated and has significant clinical activity in this patient population.