Inclusion Criteria:
1. Age 18+ years.
2. Histologically proven CD20 positive Follicular non Hodgkin lymphoma (FL) grades 1-3A (i.e. classical follicular lymphoma according to the current World Health Organization classification).3
3. No previous chemotherapy, or other investigational drug for this indication apart from focal radiotherapy.
4. Stage II-IV disease (Ann Arbor criteria).
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. Measurable FDG avid disease on baseline PET/CT scan.
7. 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. (e.g., Hb, WCC or plt count below lower limit of institutional normal range).
h) Adequate bone marrow function including:
1. Haemoglobin \>8.0 g/dL
2. White cell count (WCC) ≥2000/μL
3. Neutrophils \>1.5 x 109/L
4. Platelets \>75 x 109/L at the time of study entry, unless attributed to bone marrow infiltration by lymphoma.
i) Adequate renal function with serum creatinine ≤1.5 x ULN or creatinine clearance (CrCl) ≥ 60mL/min (using Cockcroft-Gault formula, 24hr urine collection or eGFR).
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) j) 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).
k) Adequate left ventricular ejection fraction of \>45% as demonstrated on a Gated Cardiac Blood Pool Scan or echocardiogram.
l) Life expectancy \> 3 months. m) Patients of childbearing potential willing to adhere to the following contraceptive precautions.
1. Females of childbearing potential (FCBP) 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. Females must not be breastfeeding.
3. FCBP must use appropriate method(s) of contraception to avoid pregnancy for 23 weeks (30 days plus five half-lives of nivolumab) and 28 days for golcadomide post-treatment completion.
4. Men who are sexually active with FCBP 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 90 days from the last day golcadomide and refrain from donating sperm.
5. Azoospermic males and FCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, they must still undergo pregnancy testing as described in this section.
m) Written, informed consent.
Exclusion Criteria:
1. Follicular large B-cell Lymphoma (Grade 3B) transformed follicular lymphoma, other indolent lymphomas.
2. Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
3. Central nervous system, meningeal involvement or spinal cord compression by lymphoma.
4. Patients with active, known or suspected autoimmune disease. Patients with well controlled type I diabetes mellitus, coeliac disease, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, vitiligo or psoriasis not requiring systemic treatment, or other conditions not expected to recur in the absence of an external trigger are permitted to enrol.
5. Subjects with a condition requiring systemic treatment with either corticosteroids (\>10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement therapy are permitted in the absence of active autoimmune disease.
6. Past history of interstitial lung disease.
7. Prior organ transplantation or allogeneic bone marrow transplantation.
8. Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
9. Uncontrolled or severe cardiovascular disease (NYHA class III or IV heart failure; myocardial infarction within the last 6 months of study entry); unstable angina; unstable cardiac arrhythmias; clinically significant pericardial disease.
10. Any other serious active disease.
11. Any positive test result for hepatitis B or hepatitis C virus during screening indicating acute or chronic infection. Latent hepatitis B with undetectable viral load by PCR is allowable provided appropriate anti-viral prophylaxis is given as per institutional guidelines.
12. Any positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
13. Any history of severe hypersensitivity reactions to other monoclonal antibodies.
14. A history of allergy or intolerance (unacceptable AEs) to study drug components or Polysorbate-80-containing infusions.
15. Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
