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

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

Population: 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.

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

Population: 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.

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

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

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

Population: 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.

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

Time frame: Maintenance/observation Phase: 67.8 months

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

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

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])

Population: 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.

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)

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 received at least one cycle of MabThera and available with valid data for this outcome.

Time frame: Up to Induction phase (18.7 months), Maintenance phase/observation phase (67.8 months)

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 received at least one cycle of MabThera and available with valid data.

Time frame: Up to Induction phase (18.7 months), Maintenance phase/observation phase (67.8 months)

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 received at least one cycle of MabThera and available with valid data for this outcome.

Time frame: Up to Induction phase (18.7 months), Maintenance phase/observation phase (67.8 months)

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 received at least one cycle of MabThera and available with valid data.

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

Time frame: Up to 6 years

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

Time frame: Up to Induction phase (18.7 months), Maintenance phase/observation phase (67.8 months)

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

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

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

Time frame: Maintenance phase : 67.8 months

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 received at least one MabThera infusion over the maintenance therapy period. n=number of evaluable participants for each category.

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

Population: 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.

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

Population: 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.

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

Time frame: Up to 6 years

Population: 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.

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

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

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

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