Trial Outcomes & Findings for Study of Iodine-131 Anti-B1 Antibody for Patients With Non Hodgkin's Lymphoma Who Have Previously Received Rituximab (NCT NCT00996593)

NCT ID: NCT00996593

Last Updated: 2016-11-23

Results Overview

Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present), or Partial Response (PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 43 participants
• Primary outcome timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years
• Results posted on: 2016-11-23

Participant Flow

Participants received radioimmunotherapy of tositumomab (TST) and Iodine I 131 TST in 2 phases: Phase 1, dosimetric dose; Phase 2, therapeutic dose. After radioimmunotherapy, participants could have entered a 10-year Long-Term Follow-Up study (Study BEX104526; NCT00240591) for continued evaluation.

Participant milestones

Measure	TST and Iodine I 131 TST Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Dosimetric and Therapeutic Treatment STARTED	43
Dosimetric and Therapeutic Treatment COMPLETED	0
Dosimetric and Therapeutic Treatment NOT COMPLETED	43
Long-Term Follow-Up STARTED	9
Long-Term Follow-Up COMPLETED	6
Long-Term Follow-Up NOT COMPLETED	3

Reasons for withdrawal

Measure	TST and Iodine I 131 TST Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Dosimetric and Therapeutic Treatment Lost to Follow-up	7
Dosimetric and Therapeutic Treatment Withdrawal by Subject	3
Dosimetric and Therapeutic Treatment Progressive Disease	22
Dosimetric and Therapeutic Treatment Death	1
Dosimetric and Therapeutic Treatment Enrolled in BEX104526	6
Dosimetric and Therapeutic Treatment Did Not Receive Any Study Drug	3
Dosimetric and Therapeutic Treatment Non-compliance	1
Long-Term Follow-Up Withdrawal by Subject	2
Long-Term Follow-Up Site Closed	1

Baseline Characteristics

Study of Iodine-131 Anti-B1 Antibody for Patients With Non Hodgkin's Lymphoma Who Have Previously Received Rituximab

Baseline characteristics by cohort

Measure	TST and Iodine I 131 TST n=40 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Age, Continuous	57.0 Years STANDARD_DEVIATION 11.8 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants
Race/Ethnicity, Customized White	33 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	3 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants
Race/Ethnicity, Customized Black	3 participants n=5 Participants

PRIMARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: Intent-to-Treat (ITT) Exposed Population: all participants who were enrolled into the study and received at least one dose of study drug. Only those participants evaluable for confirmed response were analyzed.

Responses had to be confirmed by 2 separate evaluations occurring >=4 weeks apart. Par. with confirmed response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present), or Partial Response (PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions).

Outcome measures

Measure

TST and Iodine I 131 TST n=34 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.

Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator

26 participants

PRIMARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population. Only those participants evaluable for confirmed response were analyzed.

CR is defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease.

Outcome measures

Measure

TST and Iodine I 131 TST n=34 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.

Number of Participants With Confirmed Complete Response (CR) as Assessed by the Investigator

9 participants

PRIMARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population. Only those participants evaluable for CR + CCR were analyzed.

CCR is defined as the complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present. Generally, an unchanging lesion =<2 centimeters (cm) in diameter by radiographic evaluation or =<1 cm in diameter by physical examination can be considered scar tissue. The extent of disease must be unchanged or decreased upon follow-up evaluations. If the extent of disease was unchanged or if further decreases occurred for 6 months or longer, the participant was reclassified as having a CR.

Outcome measures

Measure

TST and Iodine I 131 TST n=34 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.

Number of Participants With Confirmed Complete Response Plus Clinical Complete Response (CR + CCR) as Assessed by the Investigator

15 participants

PRIMARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population. Only those participants evaluable for confirmed PR were analyzed.

Confirmed PR is defined as a >=50 percent reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions, with no new lesions.

Outcome measures

Measure

TST and Iodine I 131 TST n=34 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.

Number of Participants With Confirmed Partial Response (PR) as Assessed by the Investigator

11 participants

PRIMARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population. Only those participants with confirmed response and those who experienced progressive disease were analyzed.

Response duration is defined as the time from the first documented response until disease progression.

Outcome measures

Measure

TST and Iodine I 131 TST n=16 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.

Duration of Response for All Confirmed Responders (CR, CCR, or PR) as Assessed by the Investigator

22.2 months Interval 14.9 to The SAS procedure was not able to calculate the upper limit of the confidence interval.

PRIMARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population. Only those participants with confirmed CR and those who experienced progressive disease were analyzed.

Response duration is defined as the time from the first documented response until disease progression. Disease progression is defined as a >=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measureable lesions or the appearance of any new lesion. Individual lesions must be >2 centimeters (cm) in diameter by radiographic evaluation or >1 cm in diameter by physical examination.

Outcome measures

Measure

TST and Iodine I 131 TST n=4 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.

Duration of Response for Confirmed CR as Assessed by the Investigator

NA months The median (50% quartile) was not reached/calculated/available because there were not enough events to reach a median on the Kaplan Meier curve.

PRIMARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population. Only those participants with confirmed CR + CCR response and those who experienced progressive disease were analyzed.

Response duration is defined as the time from the first documented response until disease progression.

Outcome measures

Measure

TST and Iodine I 131 TST n=6 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.

Duration of Response for CR and CCR as Assessed by the Investigator

NA months The median (50% quartile) was not reached/calculated/available because there were not enough events to reach a median on the Kaplan Meier curve.

PRIMARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population. Only those participants with confirmed PR and those who experienced progressive disease were analyzed.

Response duration is defined as the time from the first documented response until progressive disease.

Outcome measures

Measure

TST and Iodine I 131 TST n=10 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.

Duration of Response for All Confirmed Partial Responders as Assessed by the Investigator

8.8 months Interval 4.4 to 15.9

PRIMARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: Subset of ITT Exposed Population. Only those participants who had received rituximab prior to entry into this study were evaluated.

Response corresponds to the best response evaluation (ordered by CR, CCR, and PR) and does not require subsequent confirmation. Participants with CR, CCR, or PR are considered to be responders. A prior response to rituximab refers to a CR, CCR, or PR after rituximab treatment before enrollment into Study BEX104507.

Outcome measures

Measure	TST and Iodine I 131 TST n=40 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Number of Participants With or Without (w/o) a Prior Response to Rituximab (Before Entry Into This Study) Who Were Classified as Responders in This Study Responders with prior response to Rituximab; n=16	12 participants
Number of Participants With or Without (w/o) a Prior Response to Rituximab (Before Entry Into This Study) Who Were Classified as Responders in This Study Responders w/o prior response to Rituximab; n=24	16 participants

PRIMARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: Subset of ITT Exposed Population. Only those participants who had received rituximab prior to entry into this study were evaluated. Only those participants with a response were analyzed.

Duration of response is defined as the time from the first documented response to disease progression.

Outcome measures

Measure	TST and Iodine I 131 TST n=28 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Duration of Response for All Participants Classified as Responders With or Without a Prior Response to Rituximab Responders with prior response to Rituximab; n=12	18.6 months Interval 7.2 to The SAS procedure was not able to calculate the upper limit of the confidence interval.
Duration of Response for All Participants Classified as Responders With or Without a Prior Response to Rituximab Responders w/o prior response to Rituximab; n=16	19.2 months Interval 8.8 to The SAS procedure was not able to calculate the upper limit of the confidence interval.

PRIMARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: Subset of ITT Exposed Population. Only those participants who had received rituximab prior to entry into this study were evaluated.

CR is defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease.

Outcome measures

Measure	TST and Iodine I 131 TST n=40 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Number of Participants With or Without (w/o) a Prior Response to Rituximab (Before Entry Into This Study) Who Were Classified as Having a Complete Response (CR) in This Study Responders with prior response to Rituximab; n=16	5 participants
Number of Participants With or Without (w/o) a Prior Response to Rituximab (Before Entry Into This Study) Who Were Classified as Having a Complete Response (CR) in This Study Responders w/o prior response to Rituximab; n=24	4 participants

PRIMARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: Subset of ITT Exposed Population. Only those participants who had received rituximab prior to entry into this study were evaluated. Only those participants with confirmed response were analyzed.

Duration of response is defined as the time from the first documented response to disease progression.

Outcome measures

Measure	TST and Iodine I 131 TST n=9 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Duration of Response for All Participants With CR With or Without a Prior Response to Rituximab Responders with prior response to Rituximab; n=5	47.3 months Interval 4.2 to The SAS procedure was not able to calculate the upper limit of the confidence interval.
Duration of Response for All Participants With CR With or Without a Prior Response to Rituximab Responders w/o prior response to Rituximab; n=4	NA months The median (50% quartile) was not reached/calculated/available because there were not enough events to reach a median on the Kaplan Meier curve.

PRIMARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: Subset of ITT Exposed Population. Only those participants who had received rituximab prior to entry into this study were evaluated. Only those participants with confirmed response were analyzed.

Progression-free survival is defined as the time from treatment start to the first documented occurrence of disease progression or death.

Outcome measures

Measure	TST and Iodine I 131 TST n=9 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Progression-free Survival for Participants With or Without a Prior Response to Rituximab Responders with prior response to Rituximab; n=5	13.0 months Interval 3.3 to 49.1
Progression-free Survival for Participants With or Without a Prior Response to Rituximab Responders w/o prior response to Rituximab; n=4	8.9 months Interval 5.1 to 25.6

PRIMARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population. Only those participants who experienced progression were evaluated.

Progression-free survival or time to progression is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death.

Outcome measures

Measure	TST and Iodine I 131 TST n=30 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Time to Progression of Disease or Death in All Responders, Participants With CR + CCR, and Participants With PR as Assessed by the Investigator All responders, n=30	10.4 months Interval 5.7 to 18.6
Time to Progression of Disease or Death in All Responders, Participants With CR + CCR, and Participants With PR as Assessed by the Investigator CR + CCR, n=15	NA months The median (50% quartile) was not reached/calculated/available because there were not enough events to reach a median on the Kaplan Meier curve.
Time to Progression of Disease or Death in All Responders, Participants With CR + CCR, and Participants With PR as Assessed by the Investigator PR, n=11	9.2 months Interval 5.7 to 17.7

PRIMARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population. Only those participants who died during the study and during the follow-up period were analyzed.

Overall survival is defined as the time from the treatment start date to the date of death from any cause.

Outcome measures

Measure

TST and Iodine I 131 TST n=20 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.

Overall Survival

80 months Interval 24.8 to The SAS procedure was not able to calculate the upper limit of the confidence interval.

SECONDARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the adverse event was possibly or probably related to study drug. In addition, all laboratory-derived hematologic toxicities were assumed to be possibly or probably related to study drug.

Outcome measures

Measure	TST and Iodine I 131 TST n=40 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Thrombocytopenia	3 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Absolute Neutrophil Count (ANC) <1000 cells/cm^3	16 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants White Blood Cells (WBC) <2000 cells/cm^3	15 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Platelets <50000 cells/cm^3	10 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Hemoglobin <8.0 grams/deciliter (g/dL)	5 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Pyrexia	9 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Fatigue	7 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Chills	4 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Edema Peripheral	3 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Asthenia	2 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Malaise	2 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Arthralgia	5 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Myalgia	3 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Nausea	7 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Vomiting	5 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Anaemia	4 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Neutropenia	2 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Pruritus	3 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Rash	3 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Epistaxis	3 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Productive Cough	2 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Decreased Appetite	2 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Upper Respiratory Tract Infection	3 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Myelodysplastic Syndrome/ Acute Myeloid Leukemia	2 participants
Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants Headache	3 participants

SECONDARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population

An infection is the colonization of a host organism by a parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease. Specimen samples of the body fluid are cultured for testing whether the infectious organism is present and grown in the culture media to assess the growth pattern of the organisms present in the specimen. The culture results could be positive or negative. The positive culture results indicate that the tested participant has the infection under investigation, in which case therapeutic treatment with anti-infective is required.

Outcome measures

Measure	TST and Iodine I 131 TST n=40 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Number of Participants With the Indicated Type of Infection Any Infection; n=40	22 participants
Number of Participants With the Indicated Type of Infection No Infection; n=40	18 participants
Number of Participants With the Indicated Type of Infection Meningitis; n=22	0 participants
Number of Participants With the Indicated Type of Infection Pyelonephritis; n=22	0 participants
Number of Participants With the Indicated Type of Infection Sepsis; n=22	1 participants
Number of Participants With the Indicated Type of Infection Pneumonia; n=22	5 participants
Number of Participants With the Indicated Type of Infection Endocarditis/ Pericarditis; n=22	0 participants
Number of Participants With the Indicated Type of Infection Peritonitis; n=22	0 participants
Number of Participants With the Indicated Type of Infection Other Infections; n=22	17 participants

SECONDARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population. Only those participants who had infection during the study and during the follow-up period were analyzed.

Anti-infectives are capable of acting against infection, by inhibiting the spread of an infectious agent or by killing the infectious agent outright. Anti-infective is a general term that encompasses antibacterials, antibiotics, antifungals, antiprotozoans, and antivirals.

Outcome measures

Measure	TST and Iodine I 131 TST n=22 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Number of Participants With an Infection for Which Anti-infectives Were Administered Anti-infective Administered	19 participants
Number of Participants With an Infection for Which Anti-infectives Were Administered Anti-infective Not Administered	3 participants

SECONDARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population. All participants who experienced any SAE were analyzed.

An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. Medical events that may not result in death, be life-threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the investigator's medical judgement.

Outcome measures

Measure	TST and Iodine I 131 TST n=13 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Number of Participants With Serious Adverse Events (SAE) Related to Study Drug Myelodysplastic syndrome/Acute myeloid leukemia	2 participants
Number of Participants With Serious Adverse Events (SAE) Related to Study Drug Malignant hepatobiliary neoplasm	1 participants
Number of Participants With Serious Adverse Events (SAE) Related to Study Drug Squamous cell carcinoma	1 participants
Number of Participants With Serious Adverse Events (SAE) Related to Study Drug Tumor lysis syndrome	1 participants
Number of Participants With Serious Adverse Events (SAE) Related to Study Drug Pyrexia	1 participants
Number of Participants With Serious Adverse Events (SAE) Related to Study Drug Anemia	1 participants

SECONDARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population

Nadir is defined as the lowest laboratory value recorded following the administration of the study medication. Time to recovery to baseline in hematologic laboratory evaluations is the time required for recovery from nadir values to baseline values.

Outcome measures

Measure	TST and Iodine I 131 TST n=40 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations Time to nadir ANC, n=40	43.5 days Interval 3.0 to 90.0
Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations Time to nadir hemoglobin, n=40	43 days Interval 3.0 to 88.0
Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations Time to nadir platelets, n=40	34.5 days Interval 3.0 to 58.0
Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations Time to nadir WBC count, n=40	43 days Interval 3.0 to 90.0
Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations Time to recovery to baseline ANC, n=32	71 days Interval 58.0 to 76.0
Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations Time to recovery to baseline hemoglobin, n=29	74 days Interval 43.0 to 83.0
Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations Time to recovery to baseline platelets, n=29	55 days Interval 50.0 to 71.0
Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations Time to recovery to baseline WBC count, n=28	78 days Interval 71.0 to 85.0

SECONDARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population

Nadir is defined as the lowest laboratory value recorded following the administration of study medication. ANC is a measure of the number of neutrophil granulocytes present in the blood. Neutrophils are a type of white blood cell that fights against infection.

Outcome measures

Measure

TST and Iodine I 131 TST n=40 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.

Nadir Values for ANC, a Hematologic Parameter

1.2 cells/millimeters cubed (mm^3) Interval 0.0 to 6.0

SECONDARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population

Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells.

Outcome measures

Measure

TST and Iodine I 131 TST n=40 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.

Nadir Values for Hemoglobin, a Hematologic Parameter

11 G/dL Interval 7.0 to 14.0

SECONDARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population

Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Platelets and WBCs are types of blood cells.

Outcome measures

Measure	TST and Iodine I 131 TST n=40 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Nadir Values for Hematologic Parameters Platelets and WBC Count Platelets (10000 cells/microliter)	84.5 cells/microliter Interval 9.0 to 168.0
Nadir Values for Hematologic Parameters Platelets and WBC Count WBC count (1000 cells/microliter)	2.3 cells/microliter Interval 1.0 to 7.0

SECONDARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population

Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event.

Outcome measures

Measure	TST and Iodine I 131 TST n=40 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities ANC	16 participants
Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities Hemoglobin	5 participants
Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities Platelets	10 participants
Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities WBC count	15 participants

SECONDARY outcome

Timeframe: Participants were evaluated until death (up to 80.2 months in Study BEX104507) or were followed in the long-term follow-up study for up to 10.5 years

Population: ITT Exposed Population. All participants with Grade 3 or Grade 4 hematologic toxicities were analyzed.

Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event.

Outcome measures

Measure	TST and Iodine I 131 TST n=40 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities ANC, n=16	14 days Interval 7.0 to 327.0
Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities Hemoglobin, n=5	28 days Interval 11.0 to 71.0
Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities Platelets, n=10	25 days Interval 8.0 to 48.0
Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities WBC count, n=15	11 days Interval 7.0 to 235.0

Adverse Events

TST and Iodine I 131 TST

Serious events: 13 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Measure	TST and Iodine I 131 TST n=40 participants at risk Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant hepatobiliary neoplasm	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm skin	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Metabolism and nutrition disorders Hypercalcaemia	7.5% 3/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Metabolism and nutrition disorders Tumour lysis syndrome	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
General disorders Oedema	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
General disorders Pyrexia	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Infections and infestations Pneumonia	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Infections and infestations Staphylococcal sepsis	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Respiratory distress	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Blood and lymphatic system disorders Anaemia	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Cardiac disorders Arrhythmia	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Investigations Human anti-mouse antibody positive	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Musculoskeletal and connective tissue disorders Pain in extremity	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Nervous system disorders Neuropathy peripheral	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Psychiatric disorders Confusional state	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Psychiatric disorders Hallucination	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Renal and urinary disorders Renal failure acute	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Vascular disorders Deep vein thrombosis	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Vascular disorders Hypotension	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.

Other adverse events

Measure	TST and Iodine I 131 TST n=40 participants at risk Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
General disorders Fatigue	30.0% 12/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
General disorders Pyrexia	27.5% 11/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
General disorders Chills	10.0% 4/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
General disorders Asthenia	7.5% 3/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
General disorders Oedema peripheral	7.5% 3/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
General disorders Malaise	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
General disorders Chest discomfort	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
General disorders Chest pain	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
General disorders Face oedema	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
General disorders Ill-defined disorder	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
General disorders Infusion site erythema	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
General disorders Oedema	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
General disorders Pain	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Blood and lymphatic system disorders ANC <1000 cells/mm^3	40.0% 16/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Investigations WBC < 2000 cells/mm^3	37.5% 15/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Investigations Platelets <50000 cells/mm^3	25.0% 10/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Investigations Hemoglobin <8.0 g/dL	12.5% 5/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Infections and infestations Upper respiratory tract infection	20.0% 8/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Infections and infestations Pneumonia	10.0% 4/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Infections and infestations Bronchitis	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Infections and infestations Sinusitis	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Infections and infestations Fungal skin infection	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Infections and infestations Oral herpes	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Infections and infestations Respiratory tract infection	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Infections and infestations Staphylococcal sepsis	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Infections and infestations Viral infection	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Gastrointestinal disorders Nausea	20.0% 8/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Gastrointestinal disorders Vomiting	12.5% 5/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Gastrointestinal disorders Constipation	10.0% 4/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Gastrointestinal disorders Diarrhoea	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Gastrointestinal disorders Dyspepsia	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Gastrointestinal disorders Mouth ulceration	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Gastrointestinal disorders Abdominal distension	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Gastrointestinal disorders Abdominal mass	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Gastrointestinal disorders Abdominal pain	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Gastrointestinal disorders Gastrointestinal haemorrhage	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Gastrointestinal disorders Gastrointestinal pain	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Gastrointestinal disorders Gingival bleeding	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Gastrointestinal disorders Haematochezia	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Musculoskeletal and connective tissue disorders Arthralgia	15.0% 6/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Musculoskeletal and connective tissue disorders Myalgia	12.5% 5/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Musculoskeletal and connective tissue disorders Neck pain	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Musculoskeletal and connective tissue disorders Bone pain	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Musculoskeletal and connective tissue disorders Muscular weakness	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Musculoskeletal and connective tissue disorders Pain in extremity	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Musculoskeletal and connective tissue disorders Pain in jaw	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Cough	20.0% 8/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.0% 4/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Epistaxis	7.5% 3/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Productive cough	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Haemoptysis	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Nasal congestion	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Respiratory, thoracic and mediastinal disorders Respiratory distress	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Blood and lymphatic system disorders Anaemia	12.5% 5/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Blood and lymphatic system disorders Thrombocytopenia	7.5% 3/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Blood and lymphatic system disorders Neutropenia	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Blood and lymphatic system disorders Febrile neutropenia	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Blood and lymphatic system disorders Haemolytic anaemia	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Blood and lymphatic system disorders Lymphadenopathy	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Blood and lymphatic system disorders Pancytopenia	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Skin and subcutaneous tissue disorders Rash	12.5% 5/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Skin and subcutaneous tissue disorders Pruritus	7.5% 3/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Skin and subcutaneous tissue disorders Hyperhidrosis	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Skin and subcutaneous tissue disorders Rash follicular	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Skin and subcutaneous tissue disorders Rash pruritic	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Skin and subcutaneous tissue disorders Skin disorder	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Skin and subcutaneous tissue disorders Skin lesion	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Skin and subcutaneous tissue disorders Skin ulcer	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Metabolism and nutrition disorders Decreased appetite	7.5% 3/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Metabolism and nutrition disorders Hypercalcaemia	7.5% 3/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Metabolism and nutrition disorders Dehydration	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Metabolism and nutrition disorders Hypovolaemia	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Metabolism and nutrition disorders Tumour lysis syndrome	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Nervous system disorders Headache	10.0% 4/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Nervous system disorders Dizziness	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Nervous system disorders Neuropathy peripheral	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Nervous system disorders Syncope	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Investigations Cardiac murmur	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Investigations Body temperature increased	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Investigations Breath sounds abnormal	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Investigations Ejection fraction decreased	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Investigations Haemoglobin decreased	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Investigations Human anti-mouse antibody positive	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Investigations Platelet count decreased	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Investigations Weight decreased	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant hepatobiliary neoplasm	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm skin	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Cardiac disorders Tachycardia	7.5% 3/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Cardiac disorders Arrhythmia	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Cardiac disorders Palpitations	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Psychiatric disorders Insomnia	5.0% 2/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Psychiatric disorders Anxiety	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Psychiatric disorders Confusional state	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Psychiatric disorders Dissociation	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Psychiatric disorders Hallucination	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Vascular disorders Hypotension	7.5% 3/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Vascular disorders Deep vein thrombosis	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Vascular disorders Hot flush	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Vascular disorders Peripheral coldness	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Vascular disorders Thrombosis	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Renal and urinary disorders Pollakiuria	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Renal and urinary disorders Renal failure	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Renal and urinary disorders Renal failure acute	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Eye disorders Conjunctivitis	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.
Injury, poisoning and procedural complications Contusion	2.5% 1/40 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10.5 years.

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER