Prospective Observational Study on the Management of Patients With Relapsed or Refractory Follicular Lymphoma (OLYMPE)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02316613
• Collaborator: (none)
• Enrollment: 260
• Location: 1
• Duration (Months): 74
• Patients Per Site Per Month: 3.5

Study Details

Study Description

Brief Summary

This French national, multicenter, prospective, longitudinal, observational study will describe the treatment modalities of a cohort of patients with relapsed or refractory follicular non-Hodgkin's lymphoma, with evaluation of the cohort overall and according to the presence or not of MabThera® (rituximab) maintenance therapy. Actively participating physicians will enroll patients and collect therapeutic management data in a real-life setting up to 5 years.

Condition or Disease	Intervention/Treatment	Phase
Follicular Lymphoma	Drug: Rituximab

Study Design

• Study Type: Observational
• Actual Enrollment: 260 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: OLYMPE - Prospective Cohort Study on the Management of Patients With Relapsed Follicular Lymphoma
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

All Participants Participants with histologically confirmed, refractory/relapsed cluster of differentiation-20 (CD20) positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years. All participants received at least one cycle of rituximab (MabThera) during maintenance therapy or observation period.

Drug: Rituximab; Other Names: MabThera®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Modalities of the Therapeutic Decision Before First Study Induction Treatment Phase [Baseline]

   At study inclusion, the therapeutic management of participants was decided by either "pluri-disciplinary consultation meeting," "Only the physician in charge of the participant," "Discussion between physicians," or "Punctual consultation of an external physician." Percentage of participants with each of these modalities of therapeutic decision was reported.

2. Percentage of Participants With Treatments Prescribed Over the First Study Induction Phase [Induction Phase: 18.7 months]

   Over the first treatment induction period, participants received following therapies for the treatment of refractory/relapsed follicular non-Hodgkin's lymphoma: chemotherapy combined with MabThera, chemotherapy alone, MabThera monotherapy, and stem cell transplantation, radio-immunotherapy, or radiation therapy combined with any other treatment. Study induction treatment phase consists total of three visits (one before the first cycle, one halfway through therapy and one after the last cycle to evaluate response). Induction treatment duration ranged between <3 months to >6 months. Each participants may received more than one therapy.

3. Percentage of Participants With Chemotherapies Prescribed Over the First Study Induction Phase [Induction Phase: 18.7 months]

   Over the first study induction phase, participants received the following chemotherapy: regimen including fludarabine; regimen including aracytine - platinum salts; cyclophosphamide/hydroxydaunorubicin/oncovin/prednisone (CHOP-like); cyclophosphamide/vincristine/prednisone (CVP); regimen including ifosfamide - etoposide; and other chemotherapy. One participant could receive more than one type of chemotherapy over the first treatment induction period.

4. Percentage of Participants With MabThera as Maintenance Therapy [Maintenance/observation Phase: 67.8 months]

   During the maintenance period participants received four weekly infusion of MabThera.

5. Percentage of Participants With MabThera Maintenance Therapy and at Least One Observation Phase [Maintenance/observation Phase: 67.8 months]

   After study induction period (three visits) participants entered into either of two periods: 1. period of maintenance with MabThera followed by observation or 2. period of observation/maintenance without MabThera, followed by maintenance with MabThera.

6. Duration of MabThera Maintenance Therapy When Associated With Observation [Maintenance/observation Phase: 67.8 months]

   Duration of MabThera maintenance therapy was calculated from the end of induction period to the day before the first disease progression over the study (or to the date of last participant information if no disease progression until the end of the participant follow-up). Disease progression was based on the followings: Eastern Cooperative Oncology Group performance status; presence of B symptoms (fever 38°C in absence of infection for more than 8 days, night sweats, weight loss exceeding 10% in 6 months); evaluation of tumor mass (Groupe d'Etudes des Lymphomes Folliculaires criteria); number of nodal sites; number and location of extranodal sites; Ann-Arbor stage (I to IV); any histological documentation: type of biopsy (nodal, extranodal, bone marrow); histological type (progression of follicular non-Hodgkin's lymphomas or transformation); latest available hemoglobin, neutrophils, normal or leukemic lymphocytes, platelets, lactate dehydrogenase, and total gamma globulins level.

7. Percentage of Participants With Prescription of Injection Prophylaxis [Maintenance/observation Phase: 67.8 months]

   Participants was prescribed with either of the following infection prophylaxis treatment: anti-pneumocystosis agents, antiviral agents, or immunoglobulins.

8. Percentage of Participants With Injection Prophylaxis Treatment [Maintenance/observation Phase: 67.8 months]

   Participants received anti-pneumocystosis agents, antiviral agents, or immunoglobulins as infection prophylaxis. One participant could receive more than one infection prophylaxis treatment.

9. Percentage of Participants With Modalities of the Therapeutic Decision at First Study Disease Progression [Up to 6 years]

   The therapeutic management of participants was decided by either "pluri-disciplinary consultation meeting," "Only the physician in charge of the participant," "Discussion between physicians," or "Punctual consultation of an external physician." Percentage of participants with each of these modalities of therapeutic decision was reported.

10. Number of Participants With Therapeutic Management After the First Study Disease Progression [Up to 6 years]

    After the first disease progression the participants received chemotherapy, immunotherapy, radio immunotherapy, stem cell transplantation, or radiation therapy for therapeutic management of the refractory/relapsed follicular non-Hodgkin's lymphoma. One participant could receive more than one type of treatment after the first study disease progression.

Secondary Outcome Measures

1. Percentage of Participants With Last Induction Treatment Response [Induction Phase: 18.7 months]

   Last Induction treatment response: the last response assessment over the first study induction treatment (complete response [CR]: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CR unconfirmed: CR along with regression in lymph node mass by more than [>]75% in the sum of the products of greatest diameters [SPD]; Partial Response [PR]: greater than or equal to [>=] 50% decrease in SPD of 6 largest dominant nodes or nodal masses; Progression was 1 of the following: 1) lymphadenopathy; 2) a >=50% increase in previously noted or new appearance of hepato/splenomegaly; 3) >=50% increase in blood lymphocyte count with at least 5000 B lymphocytes/μL; 4) transformation to Richter's syndrome; or 5) occurrence of cytopenia; Stable disease [SD]: absence of necessary criteria to achieve CR or PR, but no advancement to progression) was described at the end of first study induction.

2. Percentage of Participants With Number of Disease Progressions [Up to 6 years]

   Participants with at least one disease progression after the first study induction period were reported.

3. Percentage of Participants With Disease Characteristics at First Study Disease Progression [Up to 6 years]

   Disease characteristics included (tumor burden, measured from whole body computed tomography (CT) scan. Groupe d'Etudes des Lymphomes Folliculaires (GELF) criteria defined as parameters to initiate treatment in participants with untreated follicular lymphoma, grade 1,2,or 3A; having just one of the criteria justified treatment: 1. involvement of >=3 nodal sites, each with diameter of >=3 centimeter(cm); 2. any nodal/extranodal tumor mass with diameter of >=7cm; 3. B symptoms (temperature >=38 degrees celsius or night sweats or weight loss >10% over past 6 months); 4. splenomegaly; 5. pleural effusion/peritoneal ascites; 6. cytopenia (leukocytes <1×10^9 and/or platelets <100×10^9/L. One participant could present with more than 1 GELF criterion. Ann Arbor staging was used as staging system for lymphomas (Stage I to IV); stage depended upon the place where malignant tissue was located (through biopsy, CT scan, or positron emission tomography) and on systemic symptoms due to lymphoma).

4. Progression Free Survival (PFS) [Up to 6 years]

   The PFS was defined as the time from the date of first induction treatment over the study (first treatment administration of first cycle) to the date of first disease progression or participants death or date of lymphoma transformation diagnosis.

5. Time to Next Treatment [Up to 6 years]

   Time to next treatment was calculated from the date of the end of first induction treatment administration over the study to the date of the start of next treatment after disease progression.

6. Overall Survival (OS) [Up to 6 years]

   The overall survival was defined as the time from the date of first induction treatment administration over the study to the date of participants' death or early study withdrawal. OS was calculated using Kaplan-Meier method.

7. Number of Participants Who Used MabThera [Up to Induction phase (18.7 months), Maintenance phase/observation phase (67.8 months)]

8. MabThera Regimen: Dose of MabThera [Up to Induction phase (18.7 months), Maintenance phase/observation phase (67.8 months)]

   All participants who received MabThera treatment before the first disease progression were reported.

9. MabThera Regimen: Infusion Duration [Up to Induction phase (18.7 months), Maintenance phase/observation phase (67.8 months)]

10. MabThera Regimen: Number of Cycles of MabThera [Up to Induction phase (18.7 months), Maintenance phase/observation phase (67.8 months)]

11. MabThera Regimen: Time Between Cycles [Up to Induction phase (18.7 months), Maintenance phase/observation phase (67.8 months)]

12. Percentage of Participants With Discontinuations and Modifications of MabThera During Maintenance Phase [Maintenance phase : 67.8 months]

13. Function Assessment of Chronic Illness Therapy-General (FACT-G) With Lymphoma-Specific Additional Concerns Subscale (Lym) Total Score [Up to 6 years (assessed at start, mid and end of induction [induction: 18.7 months], at each infusion during maintenance [maintenance phase: 67.8 months], and at disease progression [maximum up to 6 years])]

    The FACT-G with Lymphoma-Specific Additional Concerns Subscale (Lym) total score was calculated by adding the score obtained on the FACT-G (physical well-being, scored 0-28; social well-being, scored 0-28; functional well-being, scored 0-28; emotional well-being, scored 0-24), to the score obtained on the LYM subscale (15 items; responses to each item range from 0, "Not at all" to 4, "Very much"). Total score ranges from 0 to 168. Higher scores indicated a better participant-reported outcome/quality of life over the past week when responding to the items.

14. Number and Type of Hospitalization Associated With MabThera Perfusion [Up to 6 years]

    Number and type of hospitalization (a day hospitalization, short-lasting hospitalization, and short-stay hospitalization) was reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult patient (age >/= 18 years)

• Presenting with WHO grade 1-3, CD20-positive follicular non-Hodgkin's lymphoma, histologically confirmed at initial diagnosis

• In relapse (or refractory) after at least one line of treatment, regardless of the nature of previous treatments (chemotherapy and/or immunotherapy and/or radioimmunoconjugate therapy and/or radiation+chemotherapy) and for whom a decision was made to give salvage therapy

• Having received oral and written information about the study and having raised no objections to electronic capture and processing of his/her personal data

Exclusion Criteria:

• Patient participating in a clinical trial evaluating a new, non-commercialized cancer treatment at the time of inclusion

• Follicular lymphoma presenting with a transformation to diffuse large cell non-Hodgkin's lymphoma

• First line treatment with radiotherapy alone

• Initial abstention from treatment (decision to not treat the progression at the time of inclusion in the OLYMPE study)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Neuilly-sur-seine		France	92521

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02316613
• Other Study ID Numbers: ML20248
• First Posted: Dec 15, 2014
• Last Update Posted: Feb 25, 2016
• Last Verified: Jan 1, 2016

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Follicular; Rituximab

Study Results

Participant Flow

Pre-assignment Detail	Of 260 participants, 5 were excluded as no data available and duplicate cases (N=255; safety population) and 14 were excluded as other selection criteria not met (N=241; overall population).

Arm/Group Title	All Participants
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed cluster of differentiation-20 (CD20) positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years.
Period Title: Overall Study
STARTED	260
Safety Population	255
Overall Population	241
COMPLETED	156
NOT COMPLETED	104

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD2 0-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years.
Overall Participants	241
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.6 (11.2)
Sex: Female, Male (Count of Participants)
Female	110 45.6%
Male	131 54.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Modalities of the Therapeutic Decision Before First Study Induction Treatment Phase
Description	At study inclusion, the therapeutic management of participants was decided by either "pluri-disciplinary consultation meeting," "Only the physician in charge of the participant," "Discussion between physicians," or "Punctual consultation of an external physician." Percentage of participants with each of these modalities of therapeutic decision was reported.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Overall population: All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included. Number of participants analyzed = participants who were evaluable for this outcome measure.

Arm/Group Title	All Participants
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD2 0-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years.
Measure Participants	238
Pluri-disciplinary consultation meeting	81.9 34%
Only the physician in charge of the participants	8.4 3.5%
Discussion between physicians	6.3 2.6%
Punctual consultation of an external physician	3.4 1.4%

2. Secondary Outcome

Title	Percentage of Participants With Last Induction Treatment Response
Description	Last Induction treatment response: the last response assessment over the first study induction treatment (complete response [CR]: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CR unconfirmed: CR along with regression in lymph node mass by more than [>]75% in the sum of the products of greatest diameters [SPD]; Partial Response [PR]: greater than or equal to [>=] 50% decrease in SPD of 6 largest dominant nodes or nodal masses; Progression was 1 of the following: 1) lymphadenopathy; 2) a >=50% increase in previously noted or new appearance of hepato/splenomegaly; 3) >=50% increase in blood lymphocyte count with at least 5000 B lymphocytes/μL; 4) transformation to Richter's syndrome; or 5) occurrence of cytopenia; Stable disease [SD]: absence of necessary criteria to achieve CR or PR, but no advancement to progression) was described at the end of first study induction.
Time Frame	Induction Phase: 18.7 months

Outcome Measure Data

Analysis Population Description

Overall population: All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included. Number of participants analyzed (N)=number of participants evaluable for this outcome measure.

Arm/Group Title	All Participants
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment.
Measure Participants	227
Complete response	38.3 15.9%
Complete response not confirmed	11.5 4.8%
Partial response >=50%	31.7 13.2%
Partial response <50%	6.2 2.6%
Stability	5.3 2.2%
Progression	7.0 2.9%

3. Secondary Outcome

Title	Percentage of Participants With Number of Disease Progressions
Description	Participants with at least one disease progression after the first study induction period were reported.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

Overall population: All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included. Number of participants analyzed= those participants who entered in maintenance/observation after the first induction and before the first disease progression over the study.

Arm/Group Title	Without MabThera	MabThera as Maintenance Therapy
Arm/Group Description	Treatment without MabThera was defined as the absence of MabThera administration during maintenance therapy or observation period.	Treatment with MabThera was defined as the administration of at least one cycle of MabThera during maintenance therapy or observation period.
Measure Participants	74	127
Number of disease progressions: 0	52.7 21.9%	68.5 NaN
Number of disease progressions: 1	39.22 16.3%	22.0 NaN
Number of disease progressions: 2	6.8 2.8%	6.3 NaN
Number of disease progressions: 3	1.4 0.6%	2.4 NaN
Number of disease progressions: 4	0.0 0%	0.8 NaN

4. Secondary Outcome

Title	Percentage of Participants With Disease Characteristics at First Study Disease Progression
Description	Disease characteristics included (tumor burden, measured from whole body computed tomography (CT) scan. Groupe d'Etudes des Lymphomes Folliculaires (GELF) criteria defined as parameters to initiate treatment in participants with untreated follicular lymphoma, grade 1,2,or 3A; having just one of the criteria justified treatment: 1. involvement of >=3 nodal sites, each with diameter of >=3 centimeter(cm); 2. any nodal/extranodal tumor mass with diameter of >=7cm; 3. B symptoms (temperature >=38 degrees celsius or night sweats or weight loss >10% over past 6 months); 4. splenomegaly; 5. pleural effusion/peritoneal ascites; 6. cytopenia (leukocytes <1×10^9 and/or platelets <100×10^9/L. One participant could present with more than 1 GELF criterion. Ann Arbor staging was used as staging system for lymphomas (Stage I to IV); stage depended upon the place where malignant tissue was located (through biopsy, CT scan, or positron emission tomography) and on systemic symptoms due to lymphoma).
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

Overall population: All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included. Number of participants analyzed= participants with at least one disease progression over the study period. n=number of evaluable participant for each disease characteristics.

Arm/Group Title	Without MabThera	MabThera as Maintenance Therapy
Arm/Group Description	Treatment without MabThera was defined as the absence of MabThera administration during maintenance therapy or observation period.	Treatment with MabThera was defined as the administration of at least one cycle of MabThera during maintenance therapy or observation period.
Measure Participants	35	39
Tumor burden: Data not available (n=32, 38)	3.1 1.3%	5.3 NaN
Tumor burden: High (n=32, 38)	50.0 20.7%	42.1 NaN
Tumor burden: Low (n=32, 38)	46.9 19.5%	52.6 NaN
GELF criteria: at least 3 nodal sites (n=32, 38)	12.5 5.2%	21.1 NaN
GELF criteria: Any nodal/extra-nodal mass(n=32,38)	12.5 5.2%	18.4 NaN
GELF criteria: B symptoms (n=32, 38)	12.5 5.2%	0.0 NaN
GELF criteria: Splenomegaly (n=32, 38)	9.4 3.9%	2.6 NaN
GELF criteria: Pleural/ascites effusion (n=32, 38)	6.3 2.6%	7.9 NaN
GELF criteria: Cytopenia (n=32, 38)	6.3 2.6%	0.0 NaN
GELF criteria: None (n=32, 38)	46.9 19.5%	52.6 NaN
GELF criteria: Not available (n=32, 38)	3.1 1.3%	5.3 NaN
Ann-Arbor stage I (n=35, 39)	11.4 4.7%	15.4 NaN
Ann-Arbor stage II (n=35, 39)	14.3 5.9%	10.3 NaN
Ann-Arbor stage III (n=35, 39)	14.3 5.9%	15.4 NaN
Ann-Arbor stage IV (n=35, 39)	37.1 15.4%	33.3 NaN
Ann-Arbor stage data not available (n=35, 39)	17.1 7.1%	23.1 NaN
Ann-Arbor stage not assessable (n=35, 39)	5.7 2.4%	2.6 NaN

5. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	The PFS was defined as the time from the date of first induction treatment over the study (first treatment administration of first cycle) to the date of first disease progression or participants death or date of lymphoma transformation diagnosis.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

Overall population: All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included.

Arm/Group Title	All Participants
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years.
Measure Participants	241
Median (95% Confidence Interval) [months]	44.4

6. Secondary Outcome

Title	Time to Next Treatment
Description	Time to next treatment was calculated from the date of the end of first induction treatment administration over the study to the date of the start of next treatment after disease progression.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

Overall population: All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included.

Arm/Group Title	All Participants
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years.
Measure Participants	241
Median (95% Confidence Interval) [months]	NA

7. Secondary Outcome

Title	Overall Survival (OS)
Description	The overall survival was defined as the time from the date of first induction treatment administration over the study to the date of participants' death or early study withdrawal. OS was calculated using Kaplan-Meier method.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

Overall population: All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included.

Arm/Group Title	All Participants
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years.
Measure Participants	241
Median (95% Confidence Interval) [months]	NA

8. Secondary Outcome

Title	Number of Participants Who Used MabThera
Time Frame	Up to Induction phase (18.7 months), Maintenance phase/observation phase (67.8 months)

Outcome Measure Data

Analysis Population Description

All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included.

Arm/Group Title	All Participants	MabThera as Maintenance Therapy
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years. Participants who received MabThera treatment over the first study induction period was reported.	Treatment with MabThera was defined as the administration of at least one cycle of MabThera during maintenance therapy or observation period. Participants who received MabThera maintenance therapy after the first study induction was reported.
Measure Participants	241	127
At least one cycle of MabThera	230 95.4%	127 NaN
All cycles with MabThera (monotherapy/combination)	205 85.1%	127 NaN
At least one cycle of MabThera as monotherapy	89 36.9%	125 NaN
All cycles with MabThera as monotherapy	51 21.2%	124 NaN
At least one cycle of MabThera in combination	178 73.9%	2 NaN
All cycles with MabThera in combination	119 49.4%	1 NaN

9. Primary Outcome

Title	Percentage of Participants With Treatments Prescribed Over the First Study Induction Phase
Description	Over the first treatment induction period, participants received following therapies for the treatment of refractory/relapsed follicular non-Hodgkin's lymphoma: chemotherapy combined with MabThera, chemotherapy alone, MabThera monotherapy, and stem cell transplantation, radio-immunotherapy, or radiation therapy combined with any other treatment. Study induction treatment phase consists total of three visits (one before the first cycle, one halfway through therapy and one after the last cycle to evaluate response). Induction treatment duration ranged between <3 months to >6 months. Each participants may received more than one therapy.
Time Frame	Induction Phase: 18.7 months

Outcome Measure Data

Analysis Population Description

Overall population: All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included.

Arm/Group Title	All Participants
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years.
Measure Participants	241
Chemotherapy plus MabThera	47.7 19.8%
MabThera as monotherapy	21.2 8.8%
Stem Cells Transplantation	19.5 8.1%
Radio-immunotherapy	11.2 4.6%
Chemotherapy alone	2.9 1.2%
Radiation therapy	2.5 1%

10. Primary Outcome

Title	Percentage of Participants With Chemotherapies Prescribed Over the First Study Induction Phase
Description	Over the first study induction phase, participants received the following chemotherapy: regimen including fludarabine; regimen including aracytine - platinum salts; cyclophosphamide/hydroxydaunorubicin/oncovin/prednisone (CHOP-like); cyclophosphamide/vincristine/prednisone (CVP); regimen including ifosfamide - etoposide; and other chemotherapy. One participant could receive more than one type of chemotherapy over the first treatment induction period.
Time Frame	Induction Phase: 18.7 months

Outcome Measure Data

Analysis Population Description

Overall population: All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included.

Arm/Group Title	All Participants
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years.
Measure Participants	122
Regimen including fludarabine	45.9 19%
Regimen including aracytine - platinum salts	44.3 18.4%
CHOP-like	32.0 13.3%
CVP	13.1 5.4%
Regimen including ifosfamide - etoposide	10.7 4.4%
Other chemotherapy	23.8 9.9%

11. Primary Outcome

Title	Percentage of Participants With MabThera as Maintenance Therapy
Description	During the maintenance period participants received four weekly infusion of MabThera.
Time Frame	Maintenance/observation Phase: 67.8 months

Outcome Measure Data

Analysis Population Description

Overall population: All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included. Number of participants analyzed= those who entered in maintenance/observation after the first induction and before the first disease progression over the study.

Arm/Group Title	All Participants
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years.
Measure Participants	201
Number (95% Confidence Interval) [percentage of participants]	63.2 26.2%

12. Primary Outcome

Title	Percentage of Participants With MabThera Maintenance Therapy and at Least One Observation Phase
Description	After study induction period (three visits) participants entered into either of two periods: 1. period of maintenance with MabThera followed by observation or 2. period of observation/maintenance without MabThera, followed by maintenance with MabThera.
Time Frame	Maintenance/observation Phase: 67.8 months

Outcome Measure Data

Analysis Population Description

Overall population: All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included. Number of participants analyzed = those who received at least one MabThera infusion over the maintenance therapy period.

Arm/Group Title	All Participants
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years.
Measure Participants	127
Maintenance with MabThera followed by observation	70.9 29.4%
Observation followed by maintenance with MabThera	1.6 0.7%
Only maintenance therapy	27.6 11.5%

13. Primary Outcome

Title	Duration of MabThera Maintenance Therapy When Associated With Observation
Description	Duration of MabThera maintenance therapy was calculated from the end of induction period to the day before the first disease progression over the study (or to the date of last participant information if no disease progression until the end of the participant follow-up). Disease progression was based on the followings: Eastern Cooperative Oncology Group performance status; presence of B symptoms (fever 38°C in absence of infection for more than 8 days, night sweats, weight loss exceeding 10% in 6 months); evaluation of tumor mass (Groupe d'Etudes des Lymphomes Folliculaires criteria); number of nodal sites; number and location of extranodal sites; Ann-Arbor stage (I to IV); any histological documentation: type of biopsy (nodal, extranodal, bone marrow); histological type (progression of follicular non-Hodgkin's lymphomas or transformation); latest available hemoglobin, neutrophils, normal or leukemic lymphocytes, platelets, lactate dehydrogenase, and total gamma globulins level.
Time Frame	Maintenance/observation Phase: 67.8 months

Outcome Measure Data

Analysis Population Description

Overall population: All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included. Number of participants analyzed = those who received at least one infusion of MabThera and completed maintenance therapy with MabThera when associated with observation period.

Arm/Group Title	All Participants
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years.
Measure Participants	92
Median (Full Range) [months]	24.5

14. Primary Outcome

Title	Percentage of Participants With Prescription of Injection Prophylaxis
Description	Participants was prescribed with either of the following infection prophylaxis treatment: anti-pneumocystosis agents, antiviral agents, or immunoglobulins.
Time Frame	Maintenance/observation Phase: 67.8 months

Outcome Measure Data

Analysis Population Description

Overall population: All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included. Number of participants analyzed=all participants having had maintenance/observation period before the first study disease progression.

Arm/Group Title	All Participants
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years.
Measure Participants	201
Number [percentage of participants]	39.3 16.3%

15. Primary Outcome

Title	Percentage of Participants With Injection Prophylaxis Treatment
Description	Participants received anti-pneumocystosis agents, antiviral agents, or immunoglobulins as infection prophylaxis. One participant could receive more than one infection prophylaxis treatment.
Time Frame	Maintenance/observation Phase: 67.8 months

Outcome Measure Data

Analysis Population Description

Overall population: All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included. Number participants analyzed= all participants having had maintenance/observation period before the first study disease progression and received infection prophylaxis treatment.

Arm/Group Title	All Participants
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years.
Measure Participants	79
Anti-pneumocystosis agent	65.8 27.3%
Antiviral agents	83.5 34.6%
Immunoglobulins	26.9 11.2%

16. Primary Outcome

Title	Percentage of Participants With Modalities of the Therapeutic Decision at First Study Disease Progression
Description	The therapeutic management of participants was decided by either "pluri-disciplinary consultation meeting," "Only the physician in charge of the participant," "Discussion between physicians," or "Punctual consultation of an external physician." Percentage of participants with each of these modalities of therapeutic decision was reported.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

Overall population: All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included. Number of participants analyzed= participants with at least one disease progression over the study period.

Arm/Group Title	Without MabThera	MabThera as Maintenance Therapy
Arm/Group Description	Treatment without MabThera was defined as the absence of MabThera administration during maintenance therapy or observation period.	Treatment with MabThera was defined as the administration of at least one cycle of MabThera during maintenance therapy or observation period.
Measure Participants	35	40
Pluri-disciplinary consultation meeting	80.0 33.2%	67.5 NaN
Only physician in charge of the participant	17.1 7.1%	20.0 NaN
Discussion between physicians	2.9 1.2%	10.0 NaN
Punctual consultation with an external physician	0.0 0%	2.5 NaN

17. Primary Outcome

Title	Number of Participants With Therapeutic Management After the First Study Disease Progression
Description	After the first disease progression the participants received chemotherapy, immunotherapy, radio immunotherapy, stem cell transplantation, or radiation therapy for therapeutic management of the refractory/relapsed follicular non-Hodgkin's lymphoma. One participant could receive more than one type of treatment after the first study disease progression.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

Overall population: All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included. Number of participants analyzed= participants with at least one disease progression over the study period.

Arm/Group Title	Without MabThera	MabThera as Maintenance Therapy
Arm/Group Description	Treatment without MabThera was defined as the absence of MabThera administration during maintenance therapy or observation period.	Treatment with MabThera was defined as the administration of at least one cycle of MabThera during maintenance therapy or observation period.
Measure Participants	35	40
Missing	2 0.8%	4 NaN
Chemotherapy	24 10%	29 NaN
Immunotherapy	24 10%	27 NaN
Radio immunotherapy	0 0%	4 NaN
Stem cell transplantation	7 2.9%	7 NaN
Radiation therapy	6 2.5%	5 NaN

18. Secondary Outcome

Title	MabThera Regimen: Dose of MabThera
Description	All participants who received MabThera treatment before the first disease progression were reported.
Time Frame	Up to Induction phase (18.7 months), Maintenance phase/observation phase (67.8 months)

Outcome Measure Data

Analysis Population Description

All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included. Number of participants analyzed= participants who received at least one cycle of MabThera and available with valid data for this outcome.

Arm/Group Title	All Participants	MabThera as Maintenance Therapy
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years. Participants who received treatment with MabThera over the first study induction period was reported.	Treatment with MabThera was defined as the administration of at least one cycle of MabThera during maintenance therapy or observation period. Participants who received treatment with MabThera after the first study induction period was reported.
Measure Participants	216	125
Mean (Standard Deviation) [milligram (mg)]	661.25 (92.94)	671.15 (111.05)

19. Secondary Outcome

Title	MabThera Regimen: Infusion Duration
Time Frame	Up to Induction phase (18.7 months), Maintenance phase/observation phase (67.8 months)

Outcome Measure Data

Analysis Population Description

All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included. Number of participants analyzed= participants who received at least one cycle of MabThera and available with valid data.

Arm/Group Title	All Participants	MabThera as Maintenance Therapy
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years. Participants who received treatment with MabThera over the first study induction period was reported.	Treatment with MabThera was defined as the administration of at least one cycle of MabThera during maintenance therapy or observation period. Participants who received treatment with MabThera after the first study induction period was reported.
Measure Participants	199	103
Mean (Standard Deviation) [minutes (mn)]	168.60 (64.74)	150.25 (60.09)

20. Secondary Outcome

Title	MabThera Regimen: Number of Cycles of MabThera
Time Frame	Up to Induction phase (18.7 months), Maintenance phase/observation phase (67.8 months)

Outcome Measure Data

Analysis Population Description

All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included. Number of participants analyzed= participants who received at least one cycle of MabThera and available with valid data for this outcome.

Arm/Group Title	All Participants	MabThera as Maintenance Therapy
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years. Participants who received treatment with MabThera over the first study induction period was reported.	Treatment with MabThera was defined as the administration of at least one cycle of MabThera during maintenance therapy or observation period. Participants who received treatment with MabThera after the first study induction period was reported.
Measure Participants	230	125
Mean (Standard Deviation) [number of cycles]	4.8 (1.9)	7.6 (3.2)

21. Secondary Outcome

Title	MabThera Regimen: Time Between Cycles
Time Frame	Up to Induction phase (18.7 months), Maintenance phase/observation phase (67.8 months)

Outcome Measure Data

Analysis Population Description

All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included. Number of participants analyzed= participants who received at least one cycle of MabThera and available with valid data.

Arm/Group Title	All Participants	MabThera as Maintenance Therapy
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years. Participants who received treatment with MabThera over the first study induction period was reported.	Treatment with MabThera was defined as the administration of at least one cycle of MabThera during maintenance therapy or observation period. Participants who received treatment with MabThera after the first study induction period was reported.
Measure Participants	222	119
Mean (Standard Deviation) [days]	23.79 (12.04)	80.60 (20.69)

22. Secondary Outcome

Title	Percentage of Participants With Discontinuations and Modifications of MabThera During Maintenance Phase
Time Frame	Maintenance phase : 67.8 months

Outcome Measure Data

Analysis Population Description

All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included. Number of participants analyzed= participants who received at least one MabThera infusion over the maintenance therapy period. n=number of evaluable participants for each category.

Arm/Group Title	MabThera as Maintenance Therapy
Arm/Group Description	Treatment with MabThera was defined as the administration of at least one cycle of MabThera during maintenance therapy or observation period. Participants who received treatment with MabThera after the first study induction period was reported.
Measure Participants	123
Treatment discontinuation: Yes (n=123)	6.5 2.7%
Treatment discontinuation: No (n=123)	93.5 38.8%
At least 1 dose modification: Yes (n=121)	41.3 17.1%
At least 1 dose modification: No (n=121)	58.7 24.4%
At least 1 duration modification: Yes (n=121)	36.4 15.1%
At least 1 duration modification: No (n=121)	63.6 26.4%
Number (No.) of dose modifications: 0 (n=121)	58.7 24.4%
No. of dose modifications: 1 (n=121)	17.4 7.2%
No. of dose modifications: 2 (n=121)	10.7 4.4%
No. of dose modifications: 3 (n=121)	5.8 2.4%
No. of dose modifications: 4 (n=121)	4.1 1.7%
No. of dose modifications: 5 (n=121)	2.5 1%
No. of dose modifications: 6 (n=121)	0.8 0.3%
No. of infusion duration modifications: 0 (n=121)	63.6 26.4%
No. of infusion duration modifications: 1 (n=121)	10.7 4.4%
No. of infusion duration modifications: 2 (n=121)	5.8 2.4%
No. of infusion duration modifications: 3 (n=121)	4.1 1.7%
No of infusion duration modifications: 4 (n=121)	3.3 1.4%
No. of infusion duration modifications: 5 (n=121)	5.0 2.1%
No. of infusion duration modifications: 6 (n=121)	1.7 0.7%
No. of infusion duration modifications: 7 (n=121)	2.5 1%
No. of infusion duration modifications: 8 (n=121)	2.5 1%
No. of infusion duration modifications: 9 (n=121)	0.8 0.3%

23. Secondary Outcome

Title	Function Assessment of Chronic Illness Therapy-General (FACT-G) With Lymphoma-Specific Additional Concerns Subscale (Lym) Total Score
Description	The FACT-G with Lymphoma-Specific Additional Concerns Subscale (Lym) total score was calculated by adding the score obtained on the FACT-G (physical well-being, scored 0-28; social well-being, scored 0-28; functional well-being, scored 0-28; emotional well-being, scored 0-24), to the score obtained on the LYM subscale (15 items; responses to each item range from 0, "Not at all" to 4, "Very much"). Total score ranges from 0 to 168. Higher scores indicated a better participant-reported outcome/quality of life over the past week when responding to the items.
Time Frame	Up to 6 years (assessed at start, mid and end of induction [induction: 18.7 months], at each infusion during maintenance [maintenance phase: 67.8 months], and at disease progression [maximum up to 6 years])

Outcome Measure Data

Analysis Population Description

All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included. n=number of evaluable questionnaires for each category.

Arm/Group Title	All Participants
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years.
Measure Participants	241
Measure Total number of assessable questionnaire	666
Physical well-being (n=661)	22.14 (4.99)
Social well-being (n=660)	17.67 (5.31)
Emotional well-being (n=664)	17.30 (4.46)
Functional well-being (n=659)	15.32 (5.69)
Other worrying participants (n=662)	45.92 (8.88)
Global score (n=663)	118.11 (23.09)

24. Secondary Outcome

Title	Number and Type of Hospitalization Associated With MabThera Perfusion
Description	Number and type of hospitalization (a day hospitalization, short-lasting hospitalization, and short-stay hospitalization) was reported.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

All the participants (except duplicate cases and participants without data available) meeting all the inclusion/exclusion criteria were included.

Arm/Group Title	First Induction	Maintenance Therapy
Arm/Group Description	During the induction period participants received either MabThera monotherapy, MabThera combination therapy (chemotherapy and at least one cycle with MabThera), or all cycles performed without MabThera administration.	During maintenance therapy the participants received or did not received treatment with the MabThera.
Measure Participants	241	201
Measure cycles with MabThera	1035	951
A day hospitalization	727	934
Short-lasting hospitalization	308	15
Short-stay hospitalization	0	2

Adverse Events

Time Frame	Up to 6 years
Adverse Event Reporting Description	Safety population (all participants, except duplicate cases and participants without data available) included 255 participants, here data for 243 participants is reported as 12 participants data were not available (participants without available follow-up for adverse effects).
Arm/Group Title	All Participants
Arm/Group Description	Participants with histologically confirmed, refractory/relapsed CD20-positive follicular non-Hodgkin's lymphoma (grade IIII), whatever the first-line treatment was (chemotherapy and/or immunotherapy and/or radio-immunoconjugate and/or radiochemotherapy), and eligible for salvage treatment were observed for approximately 6 years.
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	94/243 (38.7%)
Blood and lymphatic system disorders
Neutropenia	5/243 (2.1%)
Anaemia	4/243 (1.6%)
Thrombocytopenia	4/243 (1.6%)
Febrile bone marrow aplasia	3/243 (1.2%)
Febrile neutropenia	2/243 (0.8%)
Agranulocytosis	1/243 (0.4%)
Haemolytic anaemia	1/243 (0.4%)
Leukopenia	1/243 (0.4%)
Pancytopenia	1/243 (0.4%)
Cardiac disorders
Myocardial infarction	3/243 (1.2%)
Cardiac disorder	1/243 (0.4%)
Cardiac failure	1/243 (0.4%)
Cardio-respiratory arrest	1/243 (0.4%)
Coronary artery disease	1/243 (0.4%)
Eye disorders
Blindness	1/243 (0.4%)
Optic neuropathy	1/243 (0.4%)
Gastrointestinal disorders
Dyspepsia	2/243 (0.8%)
Abdominal adhesions	1/243 (0.4%)
Colitits ulcerative	1/243 (0.4%)
Gastrointestinal haemorrhage	1/243 (0.4%)
Pancreatitis acute	1/243 (0.4%)
Peritonitis	1/243 (0.4%)
Small intestinal perforation	1/243 (0.4%)
General disorders
Pyrexia	7/243 (2.9%)
Disease progression	6/243 (2.5%)
Death	3/243 (1.2%)
General physical health deterioration	3/243 (1.2%)
Chest pain	1/243 (0.4%)
Fatigue	1/243 (0.4%)
Hypothermia	1/243 (0.4%)
Multi-organ failure	1/243 (0.4%)
Hepatobiliary disorders
Cholecystitis acute	1/243 (0.4%)
Jaundice	1/243 (0.4%)
Immune system disorders
Hypogammaglobulinaemia	3/243 (1.2%)
Infections and infestations
Lung infection	15/243 (6.2%)
Urinary tract infection	5/243 (2.1%)
Bacteraemia	4/243 (1.6%)
Bronchopulmonary aspergillosis	3/243 (1.2%)
Pneumocystis jiroveci pneumonia	3/243 (1.2%)
Septic shock	3/243 (1.2%)
Herpes zoster	2/243 (0.8%)
Abdominal infection	1/243 (0.4%)
Anal abscess	1/243 (0.4%)
Aspergillosis	1/243 (0.4%)
Bronchitis	1/243 (0.4%)
Bronchopneumonia	1/243 (0.4%)
Conjunctivitis infective	1/243 (0.4%)
Haemophilus infection	1/243 (0.4%)
Hepatitis B	1/243 (0.4%)
Onychomycosis	1/243 (0.4%)
Oropharyngeal candidiasis	1/243 (0.4%)
Pharyngitis	1/243 (0.4%)
Pneumonia	1/243 (0.4%)
Pneumonia cytomegaloviral	1/243 (0.4%)
Progressive multifocal leukoencephalopathy	1/243 (0.4%)
Pyelonephritis acuts	1/243 (0.4%)
Reiter's syndrome	1/243 (0.4%)
Tooth abscess	1/243 (0.4%)
Ureapasma infection	1/243 (0.4%)
Varicella	1/243 (0.4%)
Injury, poisoning and procedural complications
Fall	1/243 (0.4%)
Gastroenteritis radiation	1/243 (0.4%)
Spinal compression fracture	1/243 (0.4%)
Investigations
CD4 lymphocytes decreased	1/243 (0.4%)
Musculoskeletal and connective tissue disorders
Back pain	1/243 (0.4%)
Bone pain	1/243 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	4/243 (1.6%)
Myelodysplastic syndrome	4/243 (1.6%)
Lymphoma	2/243 (0.8%)
Squamous cell carcinoma	2/243 (0.8%)
Bronchial carcinoma	1/243 (0.4%)
Colon cancer	1/243 (0.4%)
Colon cancer metastic	1/243 (0.4%)
Hair follicle tumour benign	1/243 (0.4%)
Laryngeal cancer	1/243 (0.4%)
Lung adenocarcinoma	1/243 (0.4%)
Lung neoplasm malignant	1/243 (0.4%)
Metastases to liver	1/243 (0.4%)
Metastatic bronchial carcinoma	1/243 (0.4%)
Metastic malignant melanoma	1/243 (0.4%)
Neoplasm skin	1/243 (0.4%)
Prostate cancer	2/243 (0.8%)
Rectal cancer	1/243 (0.4%)
Refractory cytopenia with multilineage dysplasia	1/243 (0.4%)
Skin cancer	1/243 (0.4%)
Nervous system disorders
Encephalopathy	2/243 (0.8%)
Balance disorder	1/243 (0.4%)
VIIth nerve paralysis	1/243 (0.4%)
Renal and urinary disorders
Renal colic	1/243 (0.4%)
Renal failure acute	1/243 (0.4%)
Respiratory, thoracic and mediastinal disorders
Lung disorder	3/243 (1.2%)
Acute pulmonary oedema	1/243 (0.4%)
Bronchitis chronic	1/243 (0.4%)
Pleural effusion	1/243 (0.4%)
Pneumothorax	1/243 (0.4%)
Respiratory failure	1/243 (0.4%)
Sinus polyp	1/243 (0.4%)
Surgical and medical procedures
Inguinal hernia repair	1/243 (0.4%)
Vascular disorders
Aneurysm	1/243 (0.4%)
Arterial stenosis	1/243 (0.4%)
Cerebrovascular accident	1/243 (0.4%)
Ischaemic stroke	1/243 (0.4%)
Jugular vein thrombosis	1/243 (0.4%)
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	134/243 (55.1%)
General disorders
Pyrexia	49/243 (20.2%)
Infections and infestations
Bronchitis	47/243 (19.3%)
Herpes zoster	14/243 (5.8%)
Pharyngitis	12/243 (4.9%)
Sinusitis	12/243 (4.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.