On days 1, 8, 15 and 22 of the 1st cycle, bortezomib will be administered intravenously (through a vein) over 3-5 seconds followed by an intravenous infusion of rituximab. How long it will take to infuse the dose of rituximab is dependent upon your weight and how well you tolerate the infusion; it is estimated this first infusion may take between 3-4 hours. During subsequent cycles, bortezomib will again be given on days 1, 8, 15 and 22. However, rituximab will only be given on day 1 of each cycle.

Overall response rate at completion of bortezomib/rituximab maintenance therapy.

Overall response rate at this time point will be defined as complete response [CR] plus partial response [PR]) after 3 cycles of bortezomib/rituximab induction therapy and up to 4 cycles of maintenance for patients with previously untreated low-grade, B-cell NHL.

Complete response requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g., lactate dehydrogenase [LDH]) definitely assignable to NHL. There must also be complete disappearance of lymphoma involvement in the bone marrow (if initially present).

Partial response (PR) requires 50% decrease in SPD of the six largest dominant nodes or nodal masses and no increase in the size of the other nodes, liver, or spleen.

The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded)until the first date that recurrent or progressive disease is objectively documented.

Complete response requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g., lactate dehydrogenase [LDH]) definitely assignable to NHL. There must also be complete disappearance of lymphoma involvement in the bone marrow (if initially present).

Partial response (PR) requires 50% decrease in SPD of the six largest dominant nodes or nodal masses and no increase in the size of the other nodes, liver, or spleen.

Progressive disease (PD) requires the appearance of any new lesion or increase by > 50% in the size of previously involved sites.

Assess the safety and tolerance of bortezomib/rituximab as induction and maintenance therapy. Data will be collected for grade 3 and grade 4 adverse events experienced by patients that are determined to be at least possibly related to at least one study drug. Toxicity data for bortezomib/rituximab will be collected on day 1 of every cycle (1 cycle = 35 days) for up to 7 cycles during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following:

Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

Tissue microarray analysis from paraffin embedded tissue, gene expression profiling from frozen tissue (both from initial node biopsy collected/stored) and whole blood analysis of FCγR polymorphism

Correlation of tumor burden according to Groupe D'Etude des Lymphomes Follicularies (GELF) with recently developed Follicular Lymphoma International Prognostic Index (FLIPI) prognostic index. All patients enrolled in the study were required to have high tumor burden (HTB) as defined by GELF, where HTB is defined as representing higher risk disease and poorer outcomes than low tumor burden (LTB). Patients were put into low risk or high risk FLIPI groups. Low risk group with a score of 0-2 and high risk group with a score of 3-5.

A FLIPI score of 0 to 1 = "low risk" with a 10 year overall survival of 70%. A score of 2= "intermediate risk" with a 10 year overall survival of 50%. Finally, a score of ≥ 3 is considered "high risk" with a 10 year overall survival of 35%. Data was collected in connection with high or low risk FLIPI and Progression Free Survival (PFS) or Overall Survival (OS) and is reported as percentage patient with high/low risk that are progression free or alive.

Time to Treatment Failure (TTF) rate measured, from the time of first treatment to disease progression, relapse, second tumor, death from any cause, treatment toxicity requiring termination from the study, or for any reason treatment is discontinued permanently.

Progression Free Survival is measured from the time of first induction infusion to disease progression, relapse, second tumor, or death from any cause.

Progressive disease (PD) requires the following:

1. Appearance of any new lesion or increase by > 50% in the size of previously involved sites.
2. Increase of > 50% in the SPD from nadir measurement of all involved dominant lymph nodes and liver nodules and spleen nodules or unequivocal progression in any non measurable disease or nondominant site.
3. > 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node

Induction Part A will be 1 cycle of 35 days. On days 1, 8, 15 and 22 of the cycle, bortezomib 1.6mg/m2 will be administered intravenously (through a vein) over 3-5 seconds followed by an intravenous infusion of rituximab 375mg/m2 which may take between 3-4 hours.

Induction Part B will be up to 2 cycles of 35 days each. Bortezomib will be given on days 1, 8, 15 and 22. Rituximab will only be given on day 1 of each cycle.

Maintenance period will be up to 4 cycles where 1 cycle= 2 months. Bortezomib and Rituximab will be given on day 1 of each cycle only.

Overall response rate (ORR) after 1 cycle of bortezomib/rituximab induction therapy.

Overall response rate at this time point will be defined as complete response [CR] plus partial response [PR]) after 1 cycle of bortezomib/rituximab induction therapy for patients with previously untreated low-grade, B-cell NHL.

Complete response requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g., lactate dehydrogenase [LDH]) definitely assignable to NHL. There must also be complete disappearance of lymphoma involvement in the bone marrow (if initially present).

Partial response (PR) requires 50% decrease in SPD of the six largest dominant nodes or nodal masses and no increase in the size of the other nodes, liver, or spleen.

Overall response rate at completion of bortezomib/rituximab maintenance therapy.

Overall response rate at this time point will be defined as complete response [CR] plus partial response [PR]) after 3 cycles of bortezomib/rituximab induction therapy and up to 4 cycles of maintenance for patients with previously untreated low-grade, B-cell NHL.

Complete response requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g., lactate dehydrogenase [LDH]) definitely assignable to NHL. There must also be complete disappearance of lymphoma involvement in the bone marrow (if initially present).

Partial response (PR) requires 50% decrease in SPD of the six largest dominant nodes or nodal masses and no increase in the size of the other nodes, liver, or spleen.

The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded)until the first date that recurrent or progressive disease is objectively documented.

Complete response requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g., lactate dehydrogenase [LDH]) definitely assignable to NHL. There must also be complete disappearance of lymphoma involvement in the bone marrow (if initially present).

Partial response (PR) requires 50% decrease in SPD of the six largest dominant nodes or nodal masses and no increase in the size of the other nodes, liver, or spleen.

Progressive disease (PD) requires the appearance of any new lesion or increase by > 50% in the size of previously involved sites.

Data was not collected or analyzed for duration of response.

Assess the safety and tolerance of bortezomib/rituximab as induction and maintenance therapy. Data will be collected for grade 3 and grade 4 adverse events experienced by patients that are determined to be at least possibly related to at least one study drug. Toxicity data for bortezomib/rituximab will be collected on day 1 of every cycle (1 cycle = 35 days) for up to 7 cycles during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following:

Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

Tissue microarray analysis from paraffin embedded tissue, gene expression profiling from frozen tissue (both from initial node biopsy collected/stored) and whole blood analysis of FCγR polymorphism

Insufficient tumor samples were submitted for insufficient number of patients. No data was collected or analyzed.

Correlation of tumor burden according to Groupe D'Etude des Lymphomes Follicularies (GELF) with recently developed Follicular Lymphoma International Prognostic Index (FLIPI) prognostic index. All patients enrolled in the study were required to have high tumor burden (HTB) as defined by GELF, where HTB is defined as representing higher risk disease and poorer outcomes than low tumor burden (LTB). Patients were put into low risk or high risk FLIPI groups. Low risk group with a score of 0-2 and high risk group with a score of 3-5.

A FLIPI score of 0 to 1 = "low risk" with a 10 year overall survival of 70%. A score of 2= "intermediate risk" with a 10 year overall survival of 50%. Finally, a score of ≥ 3 is considered "high risk" with a 10 year overall survival of 35%. Data was collected in connection with high or low risk FLIPI and Progression Free Survival (PFS) or Overall Survival (OS) and is reported as percentage patient with high/low risk that are progression free or alive.

Time to Treatment Failure (TTF) rate measured, from the time of first treatment to disease progression, relapse, second tumor, death from any cause, treatment toxicity requiring termination from the study, or for any reason treatment is discontinued permanently.

Progression Free Survival is measured from the time of first induction infusion to disease progression, relapse, second tumor, or death from any cause.

Progressive disease (PD) requires the following:

1. Appearance of any new lesion or increase by > 50% in the size of previously involved sites.
2. Increase of > 50% in the SPD from nadir measurement of all involved dominant lymph nodes and liver nodules and spleen nodules or unequivocal progression in any non measurable disease or nondominant site.
3. > 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node

Overall survival (OS) will be measured from the time of first treatment to death from any cause.