The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country. Study No.: BEX14515 (RIT-II-2) Title: A randomized study of Iodine-131 Anti-B1 Antibody versus Anti-B1 Antibody in chemotherapy-relapsed/refractory low-grade or transformed low-grade non-hodgkin s Lymphoma (NHL). Rationale: The rationale for conducting this trial was based upon the results from Phase I/II and Phase II studies of tositumomab and Iodine I-131 tositumomab [/I-131 ] which demonstrated that /I-131 produced a high response rate in subjects with chemotherapy-relapsed/ refractory low-grade or transformed low-grade NHL. This study was designed to compare the safety and efficacy of with I-131 in subjects with chemotherapy-relapsed/ refractory low-grade or transformed low-grade NHL. Phase: II Study Period: 18 September 1996 to 19 April 21 Study Design: Randomized, controlled, open-label, multicenter study. Subjects who completed at least six months of follow-up in Protocol BEX14515 (formerly Corixa Protocol RIT-II-2) were enrolled in long term follow-up Protocol BEX14526 (formerly Corixa Protocol CCBX1-51), an administrative protocol, for continued radiographic response evaluations and safety evaluations every 6 months for years 3 through 5 post-treatment and annually for years 6 through 1 post-treatment. Subjects in BEX14526 were assessed for survival, disease status, subsequent therapy for NHL, and long-term safety, including the use of thyroid medication, development of hypothyroidism, human anti murine antibody (HAMA), myelodysplastic syndrome, acute myelogenous leukemia, and all other secondary malignancies. Additionally, subjects were followed for the development of any adverse event(s) deemed by the Principal Investigator as being possibly or probably related to a subject s previous treatment with Iodine I-131 tositumomab. Laboratory evaluations consisting of a thyroid stimulating hormone level and a complete blood cell count, with a differential and platelet count, were obtained annually through year 1 posttreatment. Long-term data collected under administrative Protocol BEX14526 are reported under the feeder/parent Protocol number, BEX14515 (formerly Corixa Protocol RIT-II-2). Centres: 9 study centers in the USA. Indication: Treatment of chemotherapy-relapsed/refractory low-grade or transformed low-grade NHL. Treatment: The treatments were administered by intravenous (IV) infusion). Arm A and Arm B Crossover (X-over) Dosimetric Dose: 45 mg of infused over 7 minutes (inclusive of a 1-minute flush) immediately followed by 5 millicurie (mci) (35 mg) of I-131 infused over 3 minutes (inclusive of a 1-minute flush). Therapeutic Dose: Seven to 14 days after the dosimetric dose, 45 mg of infused over 7 minutes (inclusive of a 1-minute flush) immediately followed by a subject-specific mci activity (35 mg) of I-131 to deliver the desired total body dose (TBD) infused over 3 minutes (inclusive of a 1-minute flush). The desired TBD was 65 cgy for subjects with a baseline platelet count of 1,1 149,999 cells/mm 3 and 75 cgy for subjects with a baseline platelet count 15, cells/mm 3. Obese subjects (subjects weighing more than 137% of their calculated lean body weight) were dosed based upon 137% of their calculated lean body mass. Arm B Dosimetric Dose: 45 mg of infused over 7 minutes (inclusive of a 1-minute flush) immediately followed by 35 mg of infused over 3 minutes (inclusive of a 1-minute flush).therapeutic Dose: Seven to 14 days after the dosimetric dose, 45 mg of infused over 7 minutes (inclusive of a 1-minute flush) immediately followed by 35 mg of infused over 3 minutes (inclusive of a 1-minute flush). Subjects randomized to Arm B were allowed to cross-over and receive / I-131 once their disease had progressed. Objectives: To compare the safety and efficacy of /I-131 and alone in subjects with relapsed/refractory low-grade or transformed low-grade B-cell NHL. Primary Outcome/Efficacy Variable: The primary efficacy endpoint was the comparison of the independent review panel-assessed, confirmed complete response rates between the /I-131 and the alone arms. Secondary Outcome/Efficacy Variable(s): The efficacy objectives were independent review panel assessments as follows: Confirmed response Duration of response Duration of complete response 1
Time to progression or death(progression-free survival) Survival and disease status Incidence of HAMA Incidence of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) Incidence of secondary malignancy Incidence of hypothyroidism Statistical Methods: Analyses were performed using data from all enrolled subjects (intent-to-treat [ITT]). Two-sided 95% confidence intervals (95% CIs) were calculated. All statistical tests of treatment and subgroup differences were 2-sided. P-values and CIs were presented without adjustment for multiple comparisons, multiple outcomes, or multiple looks. However, in order for the treatment differences to be significant, the p-value for the final analysis was required to be <.49 to account for any interim analyses using the Lan-DeMets implementation of the O Brien-Fleming sequential boundary technique. Fisher s exact test was used for the analysis of response rates and logrank statistic for duration measures. Disease progression was defined as a 25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions (for patients in partial response) or the appearance of any new lesion (for patients in partial or complete response). Individual lesions had to be >2 cm diameter (i.e., >4cm 2 ) by radiographic evaluation or >1 cm diameter (i.e., >1cm 2 ) by physical examination to be classified as progressive disease. Annualized incidence of MDS/AML was estimated. Annualized incidence accounted for length of follow-up by standardizing the incidence based on the person-years of follow-up. Likelihood-based 95% confidence intervals for the annualized incidence were calculated. Study Population: Male and female subjects 18 years of age with histologically confirmed, previously treated (1 to 3 prior chemotherapy regimens), low-grade or transformed low-grade NHL. Exclusion Criteria: Subjects with more than an average of 25% of the intratrabecular marrow space involved by lymphoma in bone marrow biopsy specimens as assessed microscopically within 42 days of study entry. Bilateral posterior iliac crest core biopsies are required if the percentage of intratrabecular space involved exceeds 1% in a unilateral biopsy. The mean of bilateral biopsies must be no more than 25%. Cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment within 4 weeks prior to study entry or persistent clinical evidence of toxicity. Prior stem cell transplant. Active obstructive hydronephrosis. Evidence of active infection requiring intravenous (IV) antibiotics at the time of study entry. New York Heart Association Class III or IV heart disease or other serious illness that would preclude evaluation. Prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which the subject has been disease-free for 5 years. Known HIV infection. Known brain or leptomeningeal metastases. Subjects who are pregnant or nursing. Previous allergic reactions to iodine. This does not include reactions to intravenous iodine-containing contrast materials. Prior exposure to monoclonal or polyclonal antibodies of any non-human species for either diagnostic or therapeutic purposes, including engineered chimeric and humanized antibodies. Prior radioimmunotherapy. Progressive disease within 1 year of irradiation arising in a field that has been previously irradiated with >35 cgy. De novo intermediate- or high-grade lymphoma. More than three prior chemotherapy regimens (different or identical agents). Patients enrolled in Protocol BEX14526 (formerly Corixa Protocol CCBX1-51) must have been enrolled in one of the following Corixa-sponsored clinical trials: RIT-I- (GSK Protocol BEX14728), RIT-II-1 (GSK Protocol BEX14731), RIT-II-2 (GSK Protocol BEX14515), RIT-II-4 (GSK Protocol BEX1454), or CP-97-12 (GSK Protocol BEX1457), and must have had 2 years of follow-up after Tositmomab and/or Iodine I-131 Tositumomab administration. 2
Arm A: / I-131 to /I-131 Number of Subjects: Planned, N 39 39 - Randomised in 14515, N 42 36 19 Disposition in Feeder Study 14515 Withdrawn from 14515; no follow-up in 14526, 28 (66.7) 31(86.1) 15 (79.) Withdrawn due to Adverse events, Withdrawn due to lack of efficacy (progressive disease), 2 (47.6) 29 (8.6) 11 (57.8) Withdrawn due to loss to follow-up; 4 (9.5) 1 (2.8) 1 (5.3) Withdrawn for other reasons, 4 (9.5) Patient died 1 (2.8) 3 (15.8) Disposition Long-term follow-up 14526 Entered follow-up (14526) 14 (33.3) 5 (13.9) 4 (21.1) Withdrawn from 14515; entered follow-up (14526), 7 (16.7) 4 (11.1) 3 (15.8) Completed 14515; entered follow-up (14526), 7 (16.7) 1 (2.8) 1 (5.3) Completed 1 years of Long-term follow-up (14526), 11 (26.1) 5 (13.9) 3 (15.8) Withdrawn from follow-up (14526) 3 (7,1) 1 (5.3) Patient died 3 (7.1) Lost to Follow-up 1 (5.3) Demographics Arm A: /I- 131 to /I-131 N (ITT) 42 36 19 Females: Males 19:23 18:18 8:11 Mean Age, years (SD) 56 (11.6) 55 (12.8) 6 (11.5) White, 39 (93) 33 (92) 18 (95) Primary Efficacy Results: (data cutoff date: 17 January 21) Panel-Assessed Primary Endpoint Arm A: / I-131 Confirmed complete response (CR or CCR) 14 (33) 3 (8) p-value.12 Duration of complete response, months, median (95% CI) NR (NR NR) NR (28.1 NR) p-value.495 NR = Not reached Secondary Outcome Variable(s): (data cutoff of 17 January 21) Panel-Assessed Secondary endpoints Arm A: / I-131 Confirmed response, 23 (55) 6 (17) p-value.1 Time to response, days, median (95% CI) 49 (48 54) 69 (5 9) p-value.119 Duration of response, months, median (95% CI) NR (7.4 NR) 18. (7.6 NR) p-value.677 Progression-free survival, months, median (95% CI) 6.3 (4.9 NR) 5.5 (2.9 6.) p-value Panel-Assessed Tertiary Endpoints (for Subjects in Arm B Who Crossed Over to /I-) Arm B P=.16 to /I- Confirmed complete response (CR or CCR) /19 () 8/19 (42) p-value.8 Duration of complete response, months, median (95% CI) 19.9 (13.2-NR) 3
p-value.6 Confirmed response, 3/19 (16) 13/19 (68) p-value.2 Time to response, days, median (95% CI) 69 (5 93) 54 (5 92) p-value.2 Duration of response, months, median (95% CI) 7.6 (4.8-7.8) 13.2 (1.5 NR) p-value.1 Progression-free survival, months, median (95% CI) 5.5 (2.8 6.) 12.4 (6.4 NR) p-value.1 Concordance Investigator Assessment and Mirror Panel Review Mirror Panel (Arm A, Arm B, and Arm B Crossover) Investigator Assessment Yes No Total Confirmed Complete Response Yes No Total 21 (22%) 4 (4%) 25 (26%) 2 (2%) 7 (72%) 72 (74%) 23 (24%) 74 (76%) 97 (1%) Confirmed Response Yes No Total NR = Not reached Investigator-assessed Response, Duration of Response, and Progression-free Survival (data cutoff date: 19 April 21) 39 (4%) 3 (3%) 42 (43%) Arm A: / I-131 11 (26) (13,39) 5 (5%) 5 (52%) 55 (57%) 44 (45%) 53 (55%) 97 (1%) Confirmed Complete Response, N (%, 95% CI) (95% Confidence Interval) 3 (8) (,17) Confirmed Response, N (%, 95% CI) 21 (5) 8 (22) (35, 65) (9, 36) Duration of Response, months, median (95% CI) 42 (9.-116.8) 18.5 (4.8,NR) Progression-free Survival, months, median (95% CI) 43.5 (11.1-119.8 2.9 (6.7-91.9) Overall Survival, months, median (95% CI) 71.5 (25.3,NR) 7. (3.9,NR) Investigator-assessed Response, Duration of Response, and Progression-free Survival (data cutoff date: 19 April 21) (for Subjects in Arm B Who Crossed Over to /I-) Confirmed Complete Response, N (%, 95% CI) (95% Confidence Interval) (NA) 8 (42) (2,64) Confirmed Response, N (%, 95% CI 3 (16) (, 32) 15 (79) (61, 97) Progression-free Survival, months, median (95% CI) 9.3 (6.7-12.2) 17.2 (11.-36.3) Overall Survival, months, median (95% CI) Unable to estimate 51.4 (19.3,86.4) Safety Results: Most Frequent Adverse Events On-therapy Adverse events (AEs) occurring from study entry through 12 weeks following the administration of the therapeutic dose were recorded. In addition, all AEs occurring beyond 12 weeks of the administration of the therapeutic dose that were considered by the Investigator to be possibly or probably related to study drug were recorded. Arm A: /I-131 to /I-131 Most Frequent Adverse Events On-therapy (by CoStart term; (data cutoff date: 17 January 21) Subjects with any AE(s), 42 (1) 33 (92) 19 (1) 1 most frequent AEs in each treatment group, : 4
Nausea 21 (5) 6 (17) 2 (11) WBC Grades III IV b 18 (43) 4 (11) 11 (58) Platelets Grades III IV a 15 (36) 1 (3) 9 (47) Absolute neutrophil count (ANC) Grades III IV c 14 (33) 4 (11) 11 (58) Hemoglobin Grades I IV d 29 (69) 14 (39) 13 (68) Nausea 2 (48) 6 (17) 2 (11) Asthenia 17 (4) 13 (36) 8 (42) Fever 14 (33) 8 (22) 3 (16) Rash 13 (31) 5 (14) 3 (16) Chills 1 (24) 7 (19) 3 (16) Pain 9 (21) 1 (28) 4 (21) Arthralgia 8 (19) 7 (19) 1 (5) Headache 5 (12) 7 (19) 4 (21) Cough increased 7 (17) 3 (8) 6 (32) Abdominal pain 7 (17) 3 (8) 3 (16) Infection 6 (14) 6 (17) 3 (16) Neck pain 4 (1) 3 (16) Bleeding events e 4 (1) 1 (3) 3 (16) Weight loss 2 (5) 3 (16) Dyspnea 6 (14) 1 (3) 3 (16) Pharyngitis 8 (19) 4 (11) 3 (16) Rhinitis 4 (1) 5 (14) 3 (16) a Platelets (x 1 3 cells/mm 3 ): Grade I = 75 to <15, Grade II = 5 to <75, Grade III = 25 to <5, Grade IV = <25. b WBC (x 1 3 cells/mm 3 ): Grade I = 3. to <4., Grade II = 2. to <3., Grade III = 1. to <2., Grade IV = <1.. c ANC (x 1 3 cells/mm 3 ): Grade I = 1.5 to <2., Grade II = 1. to <1.5, Grade III =.5 to <1., Grade IV = <.5. d Hemoglobin (g/dl): Grade I = 1. to <12., Grade II = 8. to <1., Grade III = 6.5 to <8., Grade IV = <6.5. e Includes COSTART terms ecchymosis, GI hemorrhage, hemorrhage, petechia, and retroperitoneal hemorrhage. Arm A: /I-131 to /I-131 Most Frequent Adverse Events On-therapy (by MedDRA term; (data cutoff date: 19 April 21) Subjects with any AE(s), 42 (1) 33 (92) 19 (1) 1 most frequent AEs in each treatment group, : 5
Nausea 21 (5) 6 (17) 2 (11) WBC Grades III IV b 18 (43) 4 (11) 11 (58) Platelets Grades III IV a 15 (36) 1 (3) 9 (47) Fatigue 16 (38) 12 (33) 8 (42) Absolute neutrophil count (ANC) Grades III IV c 14 (33) 4 (11) 11 (58) Pyrexia 12 (29) 7 (19) 3 (16) Chills 1 (24) 7 (19) 3 (16) Arthralgia 8 (19) 7 (19) 2 (11) Myalgia 8 (19) 6 (17) Upper respiratory tract infection 3 (7) 4 (11) 1 (5) Lymphadenopathy 3 (7) 4 (11) Pain 2 (5) 3 (8) 1 (5) Diarrhea 6 (14) 3 (8) 1 (5%) Pruritis 1 (2) 3 (8) 2 (11) Urticaria 1 (2) 3 (8) Nasal congestion 1 (2) 3 (8) 2 (11) Pleural effusion 1 (2) 3 (8) 1 (5) Back pain 4 (1) 3 (8) 1 (5) Bronchitis 1 (2) 3 (8) 1 (5) Dizziness 3 (7) 3 (8) Insomnia 4 (1) 3 (8) 1 (5) Decreased appetite 6 (14) 3 (8) Headache 5 (12) 7 (19) 4 (21) Myelodysplastic syndrome 4 (1) 4 (21) Hemoglobin Grades II-IV 6 (14) 3 (16) Anemia 6 (14) 3 (16) Thrombocytopenia 6 (14) 3 (16) Weight decreased 2 (5) 3 (16) Hypothyroidism 3 (7) 3 (16) Abdominal discomfort 3 (7) 2 (6) 2 (11) Dyspepsia 4 (1) 2 (11) Rash 6 (14) 2 (6) 2 (11) Dyspnea 4 (1) 1 (3) 2 (11) Sinusitus 1 (3) 2 (11) Pancytopenia 1 (2) 2 (11) Basal cell carcinoma 2 (5) 1 (3) 2 (11) Pollakiuria 1 (2) 2 (11) Human anti Murine Antibody (HAMA) Arm A: /I-131 to /I-131 Number evaluable for HAMA 41 (98) 36 (1) 18 (95) Number not evaluable for HAMA Positive at baseline assessment No baseline or follow-up assessment Conversion to HAMA positivity Positive Negative Time to HAMA positivity from First Dosimetric Dose, median days (range) 1 (2) 13 (32) 28 (68) 189. (28 379) 1 (28) 26 (72) 51. (2 181) 1 (5) 18 (1%) Myelodysplastic syndrome/acute myelogenous leukemia- Investigator Assessment Arm A and N 61 6
Number MDS 8 Person-years follow-up 37.8 Annualized incidence 2.6% 95% Confidence Interval 1.3%,5.2% Serious Adverse Events - On-therapy Serious Adverse events (SAEs) occurring from study entry through 12 weeks following the administration of the therapeutic dose were recorded. In addition, all SAEs occurring beyond 12 weeks of the administration of the therapeutic dose that were considered by the Investigator to be possibly or probably related to study drug were recorded. All SAEs (fatal and non-fatal) - On Therapy (ITT) (by CoStart term; (data cutoff date: 17 January 21) [n considered by the investigator to be related to study medication] Arm A: /I-131 X-over to /I-131 [related] -Includes both fatal and non-fatal events [related] [related] Subjects with any SAEs by Costart term 11 (26.2) [4] 4 (11.1) [2] 7 (36.8) [2] Abdomen enlarged 1 (5.3) [] Abdominal pain 1 (2.4) [] 1 (2.8) [] Back pain 1 (2.4) [] Chest pain 1 (2.8) [] Fever 1 (2.4) [1] Hypothermia 1 (2.8) [] Infection 1 (2.8) [] Injection site reaction 1 (2.8) [] Retroperitoneal hemorrhage 1 (2.8) [] Sepsis 3 (7.1) [2] 2 (5.6) [] Deep thrombophlebitis 1 (2.4) [] Endocarditis 1 (2.8) [] Hemorrhage 1 (5.3) [1] Syncope 1 (2.8) [] Cholecystitis 1 (2.4) [] Constipation 1 (2.4) [] Flatulence 1 (5.3) [] Gastrointestinal carcinoma 1 (5.3) [] Gastrointestinal hemorrhage 1 (2.4) [1] Intestinal obstruction 1 (2.4) [] Chronic leukemia 1 (5.3) [] Lymphoma like reaction 1 (5.3) [] Myeloproliferative disorder 1 (2.4) [] 2 (1.5) [1] Neutropenia 1 (2.8) [1] Pancytopenia 1 (2.4) [1] 1 (5.3) [1] Thrombocytopenia 1 (5.3) [1] Dehydration 1 (2.8) [] Peripheral edema 1 (5.3) [] Bone disorder 1 (2.4) [] Thinking abnormal 1 (2.8) [] Bronchitis 1 (5.3) [1] Dyspnea 1 (2.4) [1] 1 (5.3) [] Hemoptysis 1 (5.3) [1] Pleural effusion 1 (2.4) [] Pneumonia 1 (5.3) [1] Skin carcinoma 1 (5.3) [] Skin ulcer 1 (5.3) [] Cystitis 1 (2.8) [1] Hydronephrosis 1 (2.8) [] 7
All SAEs (fatal and non-fatal) - On Therapy (ITT) by MedDRA term; (data cutoff date: 19 April 21) [n considered by the investigator to be related to study medication] Arm A: /I-131 X-over to /I-131 [related] -Includes both fatal and non-fatal events [related] [related] Subjects with any SAEs by Preferred term 18 (43) [4] 6 (17) [2] 1 (53) [2] Myelodysplastic syndrome 4 (1) [3] 4 (21) [4] Basal cell carcinoma 2 (5) [1] 1 (3) [1] 2 (11) [1] Acute myeloid leukemia 2 (5) [2] Bacteremia 2 (5) [2] 1 (3) [] Squamous cell carcinoma 1 (2) [] 1 (5) [1] Burkitt s lymphoma 1 (2) [1] Malignant melanoma insitu 1 (2) [] Malignant mesenteric neoplasm 1 (2) [] Malignant peritoneal neoplasm 1 (2) [] Ovarian cancer 1 (2) [] Pancreatic carcinoma metastatic 1 (3) [] Renal cancer 1 (2) [1] Chronic meylomonocytic leukemia 1 (5) [1] Gastric cancer 1 (5) [] Lymphoma 1 (5) [] Skin cancer 1 (5) [] Squamous cell carcinoma of skin 1 (5) [1] Sepsis 1 (2) [] 1 (3) [] Pneumonia 1 (2) [1] 1 (5) [1] Cystitis 1 (3) [1] Device related infection 1 (3) [] Endocarditis bacterial 1 (3) [] Fungemia 1 (3) [] Proteus infection 1 (2) [1] Bronchitis 1 (5) [1] Abdominal pain 1 (3) [] Abdominal pain upper 1 (2) [1] Constipation 1 (2) [1] Gastrointestinal hemorrhage 1 (2) [1] Retroperitoneal hemorrhage 1 (3) [1] Small intestinal obstruction 1 (2) [1] Ascites 1 (5) [] Pancytopenia 1 (2) [1] 1 (5) [1] Febrile neutropenia 1 (3) [1] Thrombocytopenia 1 (5) [1] Dyspnea 1 (2) [] 1 (5) [] Pleural effusion 1 (2) [] Respiratory failure 1 (2) [] Hemoptysis 1 (5) [1] Hypothermia 1 (3) [1] Pyrexia 1 (2) [1] Ulcer 1 (5) [1] Myocardial infarction 1 (3) [1] Ventricular tachycardia 1 (3) [] Spinal cord compression 1 (2) [1] Syncope 1 (3) [1] Cholecystitis acute 1 (2) [1] 8
Dehydration 1 (3) [] Back pain 1 (2) [1] Mental status changes 1 (3) [1] Hydronephrosis 1 (3) [] Deep vein thrombosis 1 (2) [] Subdural hematoma 1 (5) [1] Weight decreased 1 (5) [] SAEs (fatal) - On-therapy (ITT) Serious adverse events (SAEs) occurring from study entry through 12 weeks following the administration of the therapeutic dose were recorded. In addition, all SAEs occurring beyond 12 weeks of the administration of the therapeutic dose that were considered by the Investigator to be possibly or probably related to study drug were recorded. SAEs (fatal) by MedDRA term; (data cutoff date: 19 April 21) Arm A /I-131 Arm B to /I-131 [related] [related] [related Subjects with SAEs (fatal), [related] 5 (12) [2] 3 (8) [] 6 (32) [4] Myelodysplastic syndrome 3 (7) [2] 3 (16) [3] Acute myeloid leukemia 1 (2) [1] Malignant mesenteric neoplasm 1 (2) [] Malignant peritoneal neoplasm 1 (2) [] Ovarian cancer 1 (2) [] Pancreatic carcinoma metastatic 1 (3) [] Respiratory failure 1 (2) [] Sepsis 1 (3) [] Ventricular tachycardia 1 (3) [] Ascites 1 (5) Chronic myelomonocytic leukemia 1 (5) [1] Gastric cancer 1 (5) [] Lymphoma 1 (5) [] Thrombocytopenia 1 (5) [1] Weight decreased 1 (5) [] Conclusion: Independent assessment (MIRROR Panel Review) of confirmed response revealed a higher confirmed complete response rate (33% vs. 8%, p=.12) in the tositumomab and Iodine I-131 tositumomab arm (radiolabelled tositumomab treatment arm) compared with the tositumomab arm (non-radiolabelled treatment arm). Long-term follow-up for 1 years based on investigator assessment revealed a longer PFS for the tositumomab and Iodine I-131 tositumomab arm (radiolabelled tositumomab treatment arm) compared with the tositumomab arm (non-radiolabelled treatment arm). Long-term follow up for 1 years showed comparable survival in the radiolabelled vs non-radiolabelled arm. Nausea, hematologic toxicity, hypothyroidism, and myelodysplastic syndrome were more common in the /I- 131 arm compared with the arm. The rate of HAMA positivity was similar for the /I-131- arm and the arm. 9