Molecular Monitoring With Circulating Tumor DNA and Nivolumab Maintenance

Inclusion Criteria:

* Patients must have a tissue diagnosis of diffuse large B cell lymphoma, with a negative PET/CT scan performed within 28 days of study enrollment, with one of the following clinical features: high risk IPI, ABC-subtype DLBCL, Double hit/ triple hit DLBCL, Ki67\>90%, or MYC translocation.
* Patients can have any number of prior therapies and any amount of time period from the last therapy as long as they have complete response as seen in PET/CT at the time of enrolment.
* Patients with prior salvage chemo-immunotherapy, radiation therapy, autologous transplantation are included
* Prior radiation therapy must be completed at least 2 weeks prior to study enrollment
* Autologous transplant must have been done 100 days prior to the study enrollment
* Age \> 18 years.
* ECOG performance status ≤ 2
* Life expectancy of at least 3 months
* A formalin fixed tissue block or equivalent of 24 slides of the tumor sample for analyses by Adaptive Sequenta and NeoGenomics must be available for analysis.
* Patients must be off cancer-directed therapy for at least 3 weeks (2 weeks for oral agents prior to day 1 of the study
* Patients must have suitable organ and marrow function as defined below

  * Absolute neutrophil count \> 500/mm3
  * Platelets \> 20,000/mm3
  * Total bilirubin \< 2.5 times the ULN
  * AST/ALT (SGOT/SGPT) \< 2 times institutional normal limits
  * Creatinine ≤1.5 times normal institutional limits OR
  * Creatinine clearance \> 40 ml/min for patients
* Ability to understand and willingness to sign a written informed consent and HIPAA consent document
* WOCBP and sexually active, non-sterile men must be willing to use acceptable method of contraception. WOCBP must agree to not get pregnant and sexually active, non-sterile men must agree not to impregnate a woman for at least 18 weeks after the last dose of nivolumab

Exclusion Criteria:

* Patients with second malignancies (except monoclonal B cells of undetermined significance, antecendant indolent non Hodgkin lymphoma, non-melanomatous skin cancers, papillary thyroid carcinomas, ductal carcinoma in-situ, superficial bladder cancer, prostate cancer or in situ cervical cancers) are excluded unless a complete remission was achieved at least 3 years prior to enrollment and no additional therapy is required or anticipated to be required during the treatment.
* Subjects with active autoimmune disease or a syndrome that requires systemic corticosteroids
* Subjects who received non-oncology vaccine therapies for prevention of infectious disease within 4 weeks of study drug administration.
* Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent
* Any contraindication to therapy with nivolumab
* Prior allogeneic transplantation
* Known hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Patients with documented cure from HCV infection will be included
* Known uncontrolled human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS). Patients with documented controlled HIV infection (CD4 \> 200 and undetectable viral load) will be included.
* Any condition requiring systemic treatment with corticosteroids (\> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled or topical steroids and adrenal replacement steroid doses \> 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease.
* History of anaphylactic reaction to monoclonal antibody therapy
* Poor psychiatric risk
* Patients receiving other investigational agents
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant or breast feeding. Refer to section 4.4 for further details