Trial Outcomes & Findings for Pivotal Study of Iodine I 131 Tositumomab for Chemotherapy-refractory Low-grade or Transformed Low-grade B-cell Non-Hodgkin's Lymphoma (NCT NCT00989664)

Last Updated: 2016-12-13

Results Overview

Par. with response are those with complete response (CR; complete resolution of all disease-related radiological abnormalities and the disappearance of all signs/symptoms related to disease), complete response unconfirmed (CRu; meets characteristics of CR, except the nodal size hasn't regressed sufficiently, or there is indeterminate bone marrow), or partial response (PR; \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions). Participants' LQCR was used as a comparator for subsequent treatment with Iodine I 131TST.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

60 participants

Primary outcome timeframe

Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Results posted on

2016-12-13

Participant Flow

Participants (par.) received radioimmunotherapy of tositumomab (TST) and Iodine I 131 TST in 2 phases (Ph.): Ph. 1, dosimetric dose; Ph. 2, therapeutic dose. Par. were evaluated until disease progression, they died, or they were on study for 2 years. Par. completing 2 years of study could enter a long-term follow-up study (BEX104526; NCT00240591).

Participant milestones

Participant milestones
Measure	TST and I 131 TST Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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	61
Dosimetric and Therapeutic Treatment COMPLETED	0
Dosimetric and Therapeutic Treatment NOT COMPLETED	61
Long-Term Follow-Up STARTED	14
Long-Term Follow-Up COMPLETED	11
Long-Term Follow-Up NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	TST and I 131 TST Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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 Non-compliant or Uncooperative	1
Dosimetric and Therapeutic Treatment Condition/Illness; Study Drug Unrelated	2
Dosimetric and Therapeutic Treatment Progressive Disease	49
Dosimetric and Therapeutic Treatment Death	1
Dosimetric and Therapeutic Treatment Enrolled into Study BEX104526	7
Dosimetric and Therapeutic Treatment Did Not Receive Study Drug	1
Long-Term Follow-Up Death	3

Baseline Characteristics

Pivotal Study of Iodine I 131 Tositumomab for Chemotherapy-refractory Low-grade or Transformed Low-grade B-cell Non-Hodgkin's Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TST and I 131 TST n=60 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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	59.4 Years STANDARD_DEVIATION 10.5 • n=5 Participants
Gender Female	22 Participants n=5 Participants
Gender Male	38 Participants n=5 Participants
Race/Ethnicity, Customized White	58 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	1 participants n=5 Participants
Race/Ethnicity, Customized Black	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Population: ITT Exposed Population

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=60 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR n=60 Participants Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Number of Participants (Par.) Receiving TST and I 131 TST With a Response >=30 Days Versus Par. With a Response >=30 Days After Their Last Qualifying Chemotherapy Regimen (LQCR), Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel	26 participants	5 participants

PRIMARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Population: ITT Exposed Population. Only those participants with complete response, complete response unconfirmed, or partial response were analyzed.

Duration of response is defined as the time from the first documented response (for par. with complete response, complete response unconfirmed, or partial response) until disease progression (DP). DP is defined as a \>=25% increase from the nadir value (lowest laboratory value recorded following administration of the study medication) of the sum of the products of the longest perpendicular diameters of all measurable 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

Outcome measures
Measure	TST and I 131 TST n=33 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR n=17 Participants Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Duration of Response for Par. Receiving TST and I 131 TST With a Response >=30 Days Versus the Number of Par. With a Response >=30 Days After Their LQCR, as Assessed by the MIRROR Panel	6.5 months Interval 3.1 to 11.3	3.5 months Interval 2.5 to 4.5

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

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

Participants with response include those with CR, CCR, or PR. Criteria for CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. Criteria for CCR: complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. Criteria for PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions.

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=59 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Number of Participants With Any Uncofirmed Response (CR, Clinical Complete Response [CCR], or PR), CR, CCR, CR+CCR, and PR), as Assessed by the Investigator Response (CR, CCR, or PR)	39 participants	—
Number of Participants With Any Uncofirmed Response (CR, Clinical Complete Response [CCR], or PR), CR, CCR, CR+CCR, and PR), as Assessed by the Investigator CR	11 participants	—
Number of Participants With Any Uncofirmed Response (CR, Clinical Complete Response [CCR], or PR), CR, CCR, CR+CCR, and PR), as Assessed by the Investigator CCR	1 participants	—
Number of Participants With Any Uncofirmed Response (CR, Clinical Complete Response [CCR], or PR), CR, CCR, CR+CCR, and PR), as Assessed by the Investigator CR+CCR	12 participants	—
Number of Participants With Any Uncofirmed Response (CR, Clinical Complete Response [CCR], or PR), CR, CCR, CR+CCR, and PR), as Assessed by the Investigator PR	27 participants	—

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Population: ITT Exposed Population. 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 CR, CCR , or PR. A confirmed response (CR/CCR/PR) had to be confirmed by a consecutive response (\>=28 days \[ 4 weeks\] later) that was the same or better. Individual confirmed response data only counts that response confirmed by the same response; thus, not all possible combinations are represented.

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=50 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Number of Participants With Any Confirmed Response (CR, CCR, or PR), Confirmed CR, Confirmed CCR, Confirmed CR+CCR, and Confirmed PR, as Assessed by Investigator Confirmed Response (CR, CCR, or PR)	30 participants	—
Number of Participants With Any Confirmed Response (CR, CCR, or PR), Confirmed CR, Confirmed CCR, Confirmed CR+CCR, and Confirmed PR, as Assessed by Investigator CR	9 participants	—
Number of Participants With Any Confirmed Response (CR, CCR, or PR), Confirmed CR, Confirmed CCR, Confirmed CR+CCR, and Confirmed PR, as Assessed by Investigator CCR	1 participants	—
Number of Participants With Any Confirmed Response (CR, CCR, or PR), Confirmed CR, Confirmed CCR, Confirmed CR+CCR, and Confirmed PR, as Assessed by Investigator CR+CCR	11 participants	—
Number of Participants With Any Confirmed Response (CR, CCR, or PR), Confirmed CR, Confirmed CCR, Confirmed CR+CCR, and Confirmed PR, as Assessed by Investigator PR	18 participants	—

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Population: ITT Exposed Population. Only those participants who experienced disease progression or died were analyzed.

Time to progression or progression-free survival is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death. Disease progression is defined as a \>=25% increase from the nadir value (lowest laboratory value recorded following administration of the study medication) of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter by radiographic evaluation or \>1 cm in diameter by physical examination.

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=54 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Time to Progression of Disease or Death, as Assessed by the Investigator	4.7 months Interval 3.3 to 5.8	—

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Population: ITT Exposed Population. Only those participants who experienced treatment failure were analyzed.

Time to treatment failure is defined as the length of time from the date of enrollment to the first incidence of treatment withdrawal, study removal, progression, and/or alternative therapy for the participant's lymphoma, or death.

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=54 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Time to Treatment Failure, as Assessed by the Investigator	4.6 months Interval 3.2 to 5.8	—

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

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

Outcome measures
Measure	TST and I 131 TST n=48 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Overall Survival	30.1 months Interval 17.1 to 39.9	—

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

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

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=59 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR n=60 Participants Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator Response (CR, CCR, or PR)	39 participants	17 participants
Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator CR	11 participants	1 participants
Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator CCR	1 participants	1 participants
Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator CR+CCR	12 participants	2 participants
Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator PR	27 participants	15 participants

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Population: ITT Exposed Population. All participants who experienced any AE related to study drug were analyzed.

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 related to study drug.

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=57 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Absolute Neutrophil Count (ANC) <1000 cells/cm^3	35 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Platelets <50000 cells/cm^3	29 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants White Blood Cells (WBC) <2000 cells/cm^3	29 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Hemoglobin <8.0 grams/deciliter (g/dL)	13 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Fatigue	27 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Pyrexia	19 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Chills	11 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Nausea	16 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Vomiting	9 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Diarrhoea	4 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Thrombocytopenia	10 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Neutropenia	9 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Anaemia	7 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Leukopenia	4 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Pruritus	8 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Rash	4 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Night sweats	3 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Cough	7 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Dyspnoea	7 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Throat irritation	4 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Productive cough	3 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Headache	5 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Dizziness	3 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Somnolence	3 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Decreased appetite	11 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Arthralgia	5 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Myalgia	5 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Pain in extremity	3 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Myelodysplastic syndrome	4 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Hypothyroidism	7 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Hypotension	5 participants	—
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants Tachycardia	3 participants	—

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Population: ITT Exposed Population. All participants who experienced Grade 3 or Grade 4 AEs were analyzed.

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=51 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants ANC <1000 cells/cm^3	35 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants Platelets <50000 cells/cm^3	29 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants WBC <2000 cells/cm^3	29 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants Hemoglobin <8.0 g/dL	13 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants Myelodysplastic syndrome	4 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants Neutropenia	9 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants Thrombocytopenia	8 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants Anaemia	4 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants Leukopenia	3 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants Dyspnoea	3 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants Pleural effusion	3 participants	—

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Population: ITT Exposed Population. All participants who experienced Grade 3 or 4 AEs related to study drug were analyzed.

AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE. The Investigator assessed whether the AE was possibly or probably related to study drug. In addition, all laboratory-derived hematologic toxicities (values outside the normal range) were assumed to be possibly or probably related to study drug.

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=46 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants ANC <1000 cells/cm^3	35 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants Platelets <50000 cells/cm^3	29 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants WBC <2000 cells/cm^3	29 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants Hemoglobin <8.0 g/dL	13 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants Neutropenia	9 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants Thrombocytopenia	8 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants Anaemia	4 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants Leukopenia	3 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants Myelodysplastic syndrome	4 participants	—

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Population: ITT Exposed Population. All participants who died during the study were analyzed.

The primary cause of death of the participants was assessed by the Investigator.

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=48 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Number of Participants With the Indicated Primary Cause of Death Progression of lymphoma	37 participants	—
Number of Participants With the Indicated Primary Cause of Death Complications related to study drug	0 participants	—
Number of Participants With the Indicated Primary Cause of Death Other	11 participants	—

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Population: ITT Exposed Population. All participants who died during the study were analyzed.

Time to death from the last dose of study drug is the time period difference between when study drug treatment stopped and when death occurred.

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=48 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Number of Participants With the Indicated Time to Death From the Last Dose of Study Drug <=30 Days	1 participants	—
Number of Participants With the Indicated Time to Death From the Last Dose of Study Drug >30 Days	47 participants	—

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Population: ITT Exposed Population. All participants who experienced fatal SAEs 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 judgment.

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=10 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Number of Participants With the Indicated Fatal Serious Adverse Events (SAE) Unrelated to Study Drug Pneumonia aspiration	1 participants	—
Number of Participants With the Indicated Fatal Serious Adverse Events (SAE) Unrelated to Study Drug Non-Hodgkins lymphoma	2 participants	—
Number of Participants With the Indicated Fatal Serious Adverse Events (SAE) Unrelated to Study Drug Encephalopathy	1 participants	—
Number of Participants With the Indicated Fatal Serious Adverse Events (SAE) Unrelated to Study Drug Dyspnea	1 participants	—

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Population: ITT Exposed Population. All participants who experienced fatal SAEs 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 AEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgement.

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=10 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Number of Participants With the Indicated Fatal SAEs Related to Study Drug Lung adenocarcinoma	1 participants	—
Number of Participants With the Indicated Fatal SAEs Related to Study Drug Myelodysplastic syndrome	2 participants	—
Number of Participants With the Indicated Fatal SAEs Related to Study Drug Encephalopathy	1 participants	—
Number of Participants With the Indicated Fatal SAEs Related to Study Drug Pulmonary hemorrhage	1 participants	—

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Population: ITT Exposed Population. All participants who experienced SAEs were analyzed.

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=19 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Number of Participants With the Indicated SAEs Related to Study Drug Dyspnoea	1 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Myelodysplastic syndrome	4 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Squamous cell carcinoma	2 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Basal cell carcinoma	1 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Colon cancer stage 0	1 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Lung adenocarcinoma	1 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Refractory anaemia with an excess of blasts	1 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Squamous cell carcinoma of skin	1 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Anaemia	2 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Leukopenia	1 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Neutropenia	1 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Chronic obstructive pulmonary disease	1 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Pulmonary haemorrhage	1 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Pneumocystis jiroveci pneumonia	1 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Pneumonia	1 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Atrial flutter	1 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Subdural haematoma	1 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Arthralgia	1 participants	—
Number of Participants With the Indicated SAEs Related to Study Drug Encephalopathy	1 participants	—

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Population: ITT Exposed Population. Only those participants who experienced any infection were analyzed.

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

Outcome measures
Measure	TST and I 131 TST n=59 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Number of Participants With the Indicated Type of Infection Any Infection; n=59	15 participants	—
Number of Participants With the Indicated Type of Infection No Infection; n=59	44 participants	—
Number of Participants With the Indicated Type of Infection Sepsis; n=15	0 participants	—
Number of Participants With the Indicated Type of Infection Pneumonia; n=15	5 participants	—
Number of Participants With the Indicated Type of Infection Other Infections; n=15	14 participants	—

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Population: ITT Exposed Population. Only those participants who had an 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

Outcome measures
Measure	TST and I 131 TST n=15 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Number of Participants With an Infection for Which Anti-infectives Were Administered Anti-infective Administered	12 participants	—
Number of Participants With an Infection for Which Anti-infectives Were Administered Anti-infective Not Administered	3 participants	—

SECONDARY outcome

Timeframe: HAMA was measured at baseline; Day5; Weeks 7, 17, 25; and then every 12 months while in study BEX104526. Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

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

The administration of murine antibodies may form HAMA. A HAMA assay was performed using the ImmunoSTRIP HAMA IgG enzyme-linked immune absorbent assay by a central laboratory (Covance Classic Laboratory Services, Indianapolis, IN). Fludarabine, a known immunosuppressant, might decrease HAMA production in addition to reducing bone marrow involvement. To be "positive," a participant had to have a positive HAMA assessment at any follow-up visit.

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=58 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Before Receiving the Dosimetric Dose) But Positive or Negative After Receiving the Dosimetric Dose Positive	5 participants	—
Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Before Receiving the Dosimetric Dose) But Positive or Negative After Receiving the Dosimetric Dose Negative	53 participants	—

SECONDARY outcome

Population: ITT Exposed Population. Participants who converted from being negative for HAMA at Baseline to being positive for HAMA following treatment were analyzed.

HAMA are human immunoglobulins with specificity for mouse immunoglobulins. HAMA assays were conducted in the laboratory to measure conversion to HAMA positivity following treatment. Time to HAMA positivity was calculated as the difference between the day on which HAMA positivity occurred and the first dosimetric dose administration day.

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=5 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Time to HAMA Positivity From the First Dosimetric Dose	279 days Interval 21.0 to 426.0	—

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

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. Grade 3/4 hematological toxicities: hemoglobin \<8.0 g/dL; platelets \<50,000 cells per millimeters (mm)\^3; ANC \<1000 cells per mm\^3; WBC \<2000 cells per mm\^3.

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=60 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities ANC	35 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities Hemoglobin	13 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities Platelets	29 participants	—
Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities WBC count	29 participants	—

SECONDARY outcome

Timeframe: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months

Population: ITT Exposed Population. Participants who were evaluable for thyroid function assessment were analyzed.

Thyroid function was determined periodically, including during follow-up, in order to assess if there was any effect of the Iodine 131 on thyroid function. Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.

Outcome measures

Outcome measures
Measure	TST and I 131 TST n=52 Participants Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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.	LQCR Participants previously treated with at least two chemotherapy regimes before enrolling in Study BEX104504
Number of Participants With Hypothyroidism Prior to Therapy and After the Therapeutic Dose Prior to therapy	8 participants	—
Number of Participants With Hypothyroidism Prior to Therapy and After the Therapeutic Dose After therapeutic dose	7 participants	—

Adverse Events

TST and I 131 TST

Serious events: 30 serious events

Other events: 59 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	TST and I 131 TST n=60 participants at risk Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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) Myelodysplastic syndrome	6.7% 4/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	5.0% 3/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer stage 0	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant ascites	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Refractory anaemia with an excess of blasts	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin cancer	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.0% 3/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Pneumonia	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Bronchitis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Device related sepsis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Pneumocystis jiroveci pneumonia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Blood and lymphatic system disorders Anaemia	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Blood and lymphatic system disorders Leukopenia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Blood and lymphatic system disorders Neutropenia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Abdominal distension	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Constipation	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Dysphagia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Nausea	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Vomiting	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Vascular disorders Deep vein thrombosis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Vascular disorders Orthostatic hypotension	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Vascular disorders Superior vena caval occlusion	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Cardiac disorders Atrial flutter	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Cardiac disorders Cardiomegaly	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Injury, poisoning and procedural complications Hip fracture	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Injury, poisoning and procedural complications Subdural haematoma	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Nervous system disorders Encephalopathy	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Renal and urinary disorders Nephropathy	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Renal and urinary disorders Renal failure	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Endocrine disorders Hypercalcaemia of malignancy	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Metabolism and nutrition disorders Dehydration	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Musculoskeletal and connective tissue disorders Arthralgia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.

Other adverse events

Other adverse events
Measure	TST and I 131 TST n=60 participants at risk Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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	48.3% 29/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
General disorders Pyrexia	36.7% 22/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
General disorders Chills	18.3% 11/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
General disorders Asthenia	10.0% 6/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
General disorders Oedema peripheral	10.0% 6/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
General disorders Chest pain	6.7% 4/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
General disorders Pain	5.0% 3/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
General disorders Chest discomfort	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
General disorders Oedema	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
General disorders Early satiety	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
General disorders Feeling cold	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
General disorders Feeling jittery	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
General disorders Hunger	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
General disorders Infusion site extravasation	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
General disorders Malaise	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
General disorders Nodule	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
General disorders Swelling	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Investigations ANC < 1,000 cells/mm^3	58.3% 35/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Investigations Platelets <50000 cells/mm^3	48.3% 29/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Investigations WBC < 2000 cells/mm^3	48.3% 29/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Investigations Hemoglobin < 8.0 g/dL	21.7% 13/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Nausea	35.0% 21/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Diarrhoea	21.7% 13/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Vomiting	20.0% 12/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Abdominal pain	13.3% 8/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Constipation	8.3% 5/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Abdominal discomfort	5.0% 3/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Abdominal pain upper	5.0% 3/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Abdominal distension	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Dyspepsia	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Abdominal pain lower	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Diverticulum	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Gastritis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Gastrooesophageal reflux disease	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Haemorrhoids	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Stomatitis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Gastrointestinal disorders Tongue ulceration	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Musculoskeletal and connective tissue disorders Myalgia	10.0% 6/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 6/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Musculoskeletal and connective tissue disorders Back pain	8.3% 5/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Musculoskeletal and connective tissue disorders Arthralgia	6.7% 4/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Musculoskeletal and connective tissue disorders Neck pain	6.7% 4/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Musculoskeletal and connective tissue disorders Groin pain	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Musculoskeletal and connective tissue disorders Joint swelling	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Musculoskeletal and connective tissue disorders Arthritis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Musculoskeletal and connective tissue disorders Bone lesion	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Musculoskeletal and connective tissue disorders Mobility decreased	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Musculoskeletal and connective tissue disorders Muscle atrophy	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Musculoskeletal and connective tissue disorders Muscle spasms	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Cough	21.7% 13/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.0% 6/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Productive cough	10.0% 6/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Nasal congestion	6.7% 4/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Throat irritation	6.7% 4/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.0% 3/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.0% 3/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Wheezing	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Asthma	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Bronchospasm	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Dysphonia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Dysphonia exertional	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Nasal oedema	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Skin and subcutaneous tissue disorders Pruritus	13.3% 8/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Skin and subcutaneous tissue disorders Night sweats	10.0% 6/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Skin and subcutaneous tissue disorders Rash	6.7% 4/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Skin and subcutaneous tissue disorders Erythema	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Skin and subcutaneous tissue disorders Urticaria	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Skin and subcutaneous tissue disorders Decubitus ulcer	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Skin and subcutaneous tissue disorders Petechiae	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Skin and subcutaneous tissue disorders Rash erythematous	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Skin and subcutaneous tissue disorders Rash vesicular	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Skin and subcutaneous tissue disorders Swelling face	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Upper respiratory tract infection	8.3% 5/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Bronchitis	6.7% 4/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Herpes zoster	5.0% 3/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Nasopharyngitis	5.0% 3/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Oral herpes	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Sinusitis	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Bronchopulmonary aspergillosis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Candidiasis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Cellulitis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Cytomegalovirus infection	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Ear infection	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Gastroenteritis viral	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Haemophilus infection	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Infection	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Influenza	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Keratitis herpetic	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Oral candidiasis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Parainfluenzae virus infection	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Pneumonia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Rash pustular	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Rhinitis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Infections and infestations Urinary tract infection	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Nervous system disorders Headache	11.7% 7/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Nervous system disorders Somnolence	10.0% 6/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Nervous system disorders Dizziness	6.7% 4/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Nervous system disorders Amnesia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Nervous system disorders Carpal tunnel syndrome	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Nervous system disorders Dysgeusia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Nervous system disorders Hypoaesthesia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Nervous system disorders Memory impairment	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Nervous system disorders Mental impairment	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Nervous system disorders Neuropathy peripheral	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Nervous system disorders Peroneal nerve palsy	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Nervous system disorders Sinus headache	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Nervous system disorders Tremor	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Nervous system disorders VIIth nerve paralysis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Blood and lymphatic system disorders Thrombocytopenia	16.7% 10/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Blood and lymphatic system disorders Neutropenia	13.3% 8/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Blood and lymphatic system disorders Anaemia	10.0% 6/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Blood and lymphatic system disorders Leukopenia	5.0% 3/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Blood and lymphatic system disorders Lymph node pain	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Blood and lymphatic system disorders Lymphadenopathy	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Blood and lymphatic system disorders Febrile neutropenia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Blood and lymphatic system disorders Lymphatic disorder	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Metabolism and nutrition disorders Decreased appetite	25.0% 15/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Metabolism and nutrition disorders Dehydration	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Metabolism and nutrition disorders Folate deficiency	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Metabolism and nutrition disorders Hypercalcaemia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Metabolism and nutrition disorders Hyperkalaemia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Metabolism and nutrition disorders Hypoglycaemia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Metabolism and nutrition disorders Hypokalaemia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Metabolism and nutrition disorders Hyponatraemia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Vascular disorders Hypotension	10.0% 6/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Vascular disorders Deep vein thrombosis	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Vascular disorders Flushing	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Vascular disorders Aortic stenosis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Vascular disorders Thrombophlebitis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Vascular disorders Thrombosis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Investigations Weight decreased	6.7% 4/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Investigations Blood pressure decreased	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Investigations Blood thyroid stimulating hormone increased	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Investigations Ejection fraction decreased	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Investigations Haemoglobin decreased	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Investigations Heart sounds abnormal	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Investigations Occult blood positive	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Investigations Respiratory rate increased	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Investigations Weight increased	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Psychiatric disorders Depression	5.0% 3/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Psychiatric disorders Anxiety	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Psychiatric disorders Insomnia	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Psychiatric disorders Boredom	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Psychiatric disorders Confusional state	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Psychiatric disorders Tearfulness	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Cardiac disorders Tachycardia	10.0% 6/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Cardiac disorders Palpitations	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Endocrine disorders Hypothyroidism	11.7% 7/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Injury, poisoning and procedural complications Upper limb fracture	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Injury, poisoning and procedural complications Contusion	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Injury, poisoning and procedural complications Febrile nonhaemolytic transfusion reaction	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Injury, poisoning and procedural complications Incisional hernia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Injury, poisoning and procedural complications Rib fracture	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Injury, poisoning and procedural complications Skin laceration	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Injury, poisoning and procedural complications Transfusion reaction	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Eye disorders Conjunctivitis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Eye disorders Diplopia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Eye disorders Dry eye	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Eye disorders Eye oedema	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Eye disorders Vision blurred	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Eye disorders Visual impairment	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Renal and urinary disorders Dysuria	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Renal and urinary disorders Hydronephrosis	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Renal and urinary disorders Micturition urgency	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Renal and urinary disorders Nocturia	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Renal and urinary disorders Renal failure	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Ear and labyrinth disorders Tinnitus	3.3% 2/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Ear and labyrinth disorders Ear pain	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Immune system disorders Multiple allergies	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myeloproliferative disorder	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.
Reproductive system and breast disorders Breast pain	1.7% 1/60 • Participants were evaluated until death or were followed in the long-term follow-up study for up to 10 years.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

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