Lenalidomide and Epcoritamab for the Treatment of Previously Untreated Follicular Lymphoma

Inclusion Criteria:

* Documented informed consent of the participant and/or legally authorized representative

  * Assent, when appropriate, will be obtained per institutional guidelines
* Age: ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) ≤ 2
* Histologically confirmed previously untreated FL grade 1-3a, requiring therapy per Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
* Radiologically measurable lymphadenopathy (\> 1.5 cm) or extranodal involvement (including spleen, bone marrow or other extranodal site)
* Without bone marrow involvement: Absolute neutrophil count (ANC) ≥ 1,000/mm\^3 With bone marrow involvement: ANC ≥ 500/mm\^3

  * NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement
* Without bone marrow involvement: Platelets ≥ 50,000/mm\^3 With bone marrow involvement: Platelets ≥ 25,000/mm\^3

  * NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement.
* Total bilirubin ≤ 2 x upper limit of normal (ULN) (unless has Gilbert's disease)
* Aspartate aminotransferase (AST) ≤ 2.5 x ULN
* Alanine aminotransferase (ALT) ≤ 2.5 x ULN
* Creatinine clearance of ≥ 45 mL/min per 24 hour urine test or the Cockcroft-Gault formula or creatinine level \< 1.5 mg/dL
* If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN
* If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
* Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test

  * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Agreement by females and males of childbearing potential\* to use an effective method of birth control (i.e., failure rate of \< 1% per year) or abstain from heterosexual activity for the course of the study treatment period through at least 30 days after the last dose of lenalidomide, and 2 months after the last dose of epcoritamab, or 4 months after the last dose of tocilizumab (if applicable) whichever is longer

  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from .menses for \> 1 year (women only)

    * All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS)® program and be willing and able to comply with the requirements of the REMS program (including use of aspirin \[ASA\]/Food and Drug Administration \[FDA\] approved blood thinner)
    * Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program

Exclusion Criteria:

* Prior therapeutic intervention with any anti-cancer agents; localized radiotherapy ≤ 20 Gy total dose is permissible if occurred ≥ 4 weeks prior to first dose of study medication.

  * Participants must have at least one non-irradiated target lesion
* Concurrent enrollment in another therapeutic investigational study
* Vaccinated with live vaccines within 4 weeks of the first dose of study drug
* Current evidence of central nervous system involvement by the lymphoma
* Grade 3b or transformed FL
* History of prior malignancy except:

  * Malignancy treated with curative intent and no known active disease present for ≥ 2 years prior to initiation of therapy on current study
  * Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease
  * Asymptomatic prostate cancer managed with "watch and wait" strategy or hormonal therapy
* Uncontrolled active systemic infection
* Absolute lymphocyte count \> 5,000/uL
* Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Patients with past HBV infection (defined as negative hepatitis B virus surface protein antigen \[HbsAg\] and positive hepatitis B core antibody \[HbcAb\]) are eligible if HBV deoxyribonucleic acid (DNA) is undetectable. Patients who are positive for HCV antibody are eligible if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). Testing to be done only in patients suspected of having infections or exposures
* Known active human immunodeficiency virus (HIV) infection. Subjects who have an undetectable or unquantifiable HIV viral load with CD4 \> 200 and are on highly active antiretroviral therapy (HAART) medication are allowed. Testing to be done only in patients suspected of having infections or exposures
* Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months of screening
* Females only: Pregnant or breastfeeding or intending to become pregnant during the study or within 6 months after the final dose of all study drugs

  * Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study drug
* Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)