Nivolumab and Combination Chemotherapy in Treating Patients with Diffuse Large B-Cell Lymphoma

Inclusion Criteria

• Patient must have a confirmed diagnosis of: * De novo DLBCL including the clinical subtypes of primary mediastinal, - cell/histiocyte-rich large B-cell lymphoma and intravascular DLBCL OR * De novo transformed DLBCL from follicular lymphoma (FL) OR * Any high grade CD20+ B-cell lymphoma per World Health Organization (WHO) 2016 OR * CD20+ aggressive B-cell lymphoma unclassifiable.
• Patient must be deemed an appropriate candidate for R-CHOP therapy.
• Patients must be naive to prior therapy for the study diagnosis. Palliative steroids for symptom management prior to study treatment are allowed with at 7 day washout prior to dosing lead-in nivolumab.
• Patient must have advanced stage III/IV OR early stage disease where provider determines single modality therapy with chemo-immunotherapy is most appropriate (i.e radiation deferred).
• Patient must have measurable disease (defined as >= 1.5 cm in diameter) with correlated fludeoxyglucose F-18 (FDG)-avidity on positron emission tomography (PET) scan.
• Patient must have Eastern Cooperative Oncology Group (ECOG) performance status =< 2.
• Absolute neutrophil count (ANC) >= 1000/mm^3, independent of growth factor support or >= 500/mm^3 in cases of ongoing bone marrow involvement (in either case, these must be independent of transfusion support) documented =< 28 days prior to registration.
• Platelets >= 100,000/mm^3, or >= 50,000 in cases of ongoing bone marrow involvement (In either case, these must be independent of transfusion support) documented =< 28 days prior to registration.
• Total bilirubin =< 1.5 x upper limit of normal (ULN) documented =< 28 days prior to registration.
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) /alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SPGT]) =< 3 x ULN documented =< 28 days prior to registration.
• Creatinine clearance >= 25 mL/min (using Cockcroft gault equation) documented =< 28 days prior to registration.
• Females of child-bearing potential (FOCBP) and men who are sexually active with FOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment and the designated post-treatment period. * NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: ** Has not undergone a hysterectomy or bilateral oophorectomy. ** Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months).
• Females of childbearing potential (FOCBP) must have a negative urine or serum pregnancy test within 28 days prior to registration on study.
• Patients must have the ability to understand and willingness to sign a written informed consent prior to registration on study.

Exclusion Criteria

• Patients who have received prior therapy intended to treat the study diagnosis are not eligible.
• Patients who have received prior anti-PD-1/L1 therapy for any indication are not eligible.
• Patients who require urgent cytoreductive therapy (e.g. surgery or radiation) are not eligible.
• Subjects with known immunodeficiency, known autoimmune disease, or concurrent use of immunomodulatory agents are not eligible.
• Patients who have another condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications =< 14 days prior to registration are not eligible. * NOTE: Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by a contact allergen) is permitted. Additionally, palliative steroids for management of symptoms related to lymphoma are allowed prior to initiation of study treatment with a 7 day washout required prior to dosing lead-in nivolumab.
• Patients with known central nervous system (CNS) involvement are not eligible.
• Patients with an active malignancy requiring therapy such as radiation, chemotherapy, or immunotherapy are not eligible. * NOTE: Exceptions to this are as follows: localized non-melanotic skin cancer and any cancer that in the judgment of the investigator has been treated with curative intent and will not interfere with the study treatment plan and response assessment. Prostate and breast cancer patients undergoing hormone therapy with no currently active disease are eligible.
• Patients with known human immunodeficiency virus (HIV) are not eligible.
• Patients with clinically active hepatitis B or C infections are not eligible. * NOTE: Patients with a history of hepatitis may be eligible if they have a normal titer. Such cases should be approved by the study principal investigator (PI).
• Patients who have any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator’s opinion, could compromise the subject’s safety or put the study outcomes at risk are not eligible.
• Pregnant or nursing females are not eligible.
• Patients with uncontrolled intercurrent illness including, but not limited to, any of the following are not eligible: * Ongoing or active systemic infection. * Symptomatic congestive heart failure. * Myocardial infarction within 6 months prior to registration. * Unstable angina pectoris. * Uncontrolled or symptomatic cardiac arrhythmias. * Any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional classification. * Psychiatric illness/social situations that would limit compliance with study requirements.