1st FLOR: This phase I trial is trying to determine whether it is safe to give the drug Nivolumab before and in combination with the drug Rituximab, in patients who have previously untreated Follicular LymphomaFirst-line Treatment for Grade 1-3A Follicular Lymphoma Using Opdivo (Nivolumab) Plus Rituximab

Inclusion

1. Age ≥ 18 years.
2. Histologically proven Follicular non Hodgkin lymphoma (FL) grades 1-3A according to the current World Health Organization classification.29 The B cell nature of the proliferation must be verified by the positivity with an anti-CD20 antibody.
3. No previous chemotherapy, or other investigational drug for this indication apart from focal radiotherapy.
4. Stage II-IV disease (Ann Arbor criteria). Stage II disease must not be encompassable in a single radiotherapy field and being considered for definitive radiotherapy.
5. Eastern Collaborative Oncology Group (ECOG) performance status 0 to 1 unless attributable to lymphoma, in which case patients of performance status 2 are also eligible.
6. Deemed to need treatment by treating investigator. Reasons for treatment can include, but are not limited to:

a. Any nodal or extranodal tumour mass >7cm AND/OR multiple extranodal disease sites b. Involvement of at least 3 sites each with diameter >3cm c. Symptomatic splenic enlargement d. Organ involvement/compression e. Ascites or pleural effusion f. Lactate Dehydrogenase (LDH) elevated g. Presence of systemic symptoms h. Disease progression in preceding 3 months i. Evidence of marrow infiltration with marrow compromise. (eg Hb, WBC or plt count below lower limit of institutional normal range).

g) Adequate bone marrow function including:

1. Haemoglobin >9.0 g/dL
2. White blood cells (WBC) ≥2000/μL
3. Neutrophils >1.5 x 109/L
4. Platelets >100 x 109/L at the time of study entry, unless attributed to bone marrow infiltration by lymphoma.

h) Adequate renal function with serum creatinine ≤1.5 x ULN or creatinine clearance (CrCl) ≥ 40mL/min (using Cockroft-Gault formula) Female CrCl = (140 - age in years) x weight (kg) x 0.85 72 x serum creatinine (mg/dL) Male CrCl = (140 - age in years) x weight (kg) x 1.00 72 x serum creatinine (mg/dL) i) Adequate hepatic function with AST/ALT ≤3x ULN and total bilirubin ≤1.5 x ULN (except subjects with Gilbert syndrome, who can have a total bilirubin ≤3 mg/dL or ≤51.3 μmol/L) j) Life expectancy > 3 months. k) Patients of childbearing potential willing to adhere to contraceptive precautions

1. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment
2. Women must not be breastfeeding
3. WOCBP must use appropriate method(s) of contraception to avoid pregnancy for 23 weeks (30 days plus five half-lives of nivolumab) post-treatment completion
4. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. They must agree to adhere to contraception for a period of 31 weeks after the last day of nivolumab.
5. Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, they must still undergo pregnancy testing as described in this section.

l) Written, informed consent.