Tafasitamab and Rituximab for the Treatment of Newly Diagnosed Follicular Lymphoma

Inclusion Criteria: * Age ≥ 18 years old * Patients must have histologic confirmation of follicular lymphoma (FL) (grade 1, 2, and 3A or classic follicular lymphoma) * Meeting any one of the following criteria for therapy initiation: * Involvement of ≥ 3 nodal sites, each with diameter of ≥ 3 cm. * Any nodal or extranodal tumor mass with a diameter of ≥ 7 cm. * B symptoms (fever ≥ 38 degrees Celsius of unclear etiology, night sweats, weight loss \> 10% within the prior 6 months) attributed to FL. * Risk of local compressive symptoms that may result in organ compromise. * Splenomegaly with the inferior margin below the umbilical line or splenic lesion without splenomegaly. * Significant cytopenia (absolute neutrophil count \< 1500/mm3, platelets \< 100,000/uL, hemoglobin \< 10 g/dL) * Leukemia (\> 5,0000/uL circulating lymphocytes) * Pleural effusion or ascites attributed to lymphoma * Have measurable nodal disease, including at least 1 disease site measuring at least 1.5 cm in longest dimension on CT or fludeoxyglucose (FDG)-PET, or a FDG-avid extranodal measurable site measuring at least 1.0 cm in longest dimension. Measurable disease also includes spleen size more than 13 cm in vertical length * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Absolute neutrophil count ≥ 1500/mm\^3 (unless due to lymphoma involvement of the bone marrow or spleen) * Platelets ≥ 75,000/mm\^3 (unless due to bone marrow involvement by lymphoma) * Hemoglobin ≥ 8 g/dL (unless due to bone marrow involvement by lymphoma) * Total bilirubin ≤ 2.0 mg/dL, except for patients with documented lymphoma involvement of liver or with a known history of Gilbert's disease * Alkaline phosphatase/aspartate aminotransferase (AST)/(serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 × institutional upper limit of normal, except for patients with documented liver involvement * Creatinine clearance ≥ 30 ml/min * Fertile male and women of child bearing potential (WOCBP) patients must be willing to use highly effective contraceptive methods from study recruitment to at least 6 months after the last dose of study treatment * Ability to understand and willingness to sign a written informed consent document Exclusion Criteria: * FL grade 3B or transformed FL * Patients receiving any other investigational agents * Patients with known central nervous system involvement of lymphoma * History of a second primary malignancy that could affect compliance with the protocol or interpretation of results except with permission of the principal investigator. Malignancies treated curatively or at low-risk of progressing at the judgment of the primary investigator (PI) may be included * Known active and uncontrolled bacterial, viral, fungal, mycobacterial, or other infection at study enrollment * Uncontrolled intercurrent illness such as: history of myocardial infarction (MI) in the last 6 months, congestive heart failure New York Heart Association (NYHA) Class III-IV, uncontrolled or symptomatic arrhythmia, stroke in last 6 months, liver cirrhosis, and autoimmune disorder requiring immunosuppression or long-term corticosteroids (\> 10 mg daily prednisone equivalent) * Prior use of any monoclonal antibody within 4 weeks before the first administration * Breastfeeding or pregnant women * Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody are eligible if the corresponding polymerase chain reaction (PCR) test is negative prior to enrollment. Hepatitis B core antibody (+) patients without evidence of HBsAg or Hep B PCR (+) are eligible with appropriate Hepatitis B reactivation prophylaxis as per institutional guidelines * History of human immunodeficiency virus (HIV) infection uncles the viral load is undetectable and CD4 count is at least 400 * History or evidence of rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption * Major surgery (excluding lymph node biopsy) within 28 days prior to signing the informed consent form (ICF) unless the participant is recovered at the time of signing the ICF * Any systemic anti-lymphoma and/or investigational therapy within 28 days prior to the start of cycle 1 * Administration of a live vaccine within 28 days prior to the start of study treatment (cycle 1 day 1) * History of hypersensitivity to compounds of similar biological or chemical composition to tafasitamab, immunomodulatory drugs, rituximab, other monocolonal antibodies (mAbs), and/or the excipients contained in the study drug formulations