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