Molecular Monitoring With Circulating Tumor DNA and Nivolumab Maintenance

Primary Objective:

To determine if nivolumab administration, as a maintenance strategy in DLBCL patients with high risk of relapse, can convert positive ctDNA to negative ctDNA and/or result in relapse free survival (RFS-ctDNA) of 9 months or longer after positive ctDNA was documented.

Secondary Objectives:

• To evaluate safety of nivolumab as maintenance drug in post-induction, post-salvage and post-autologous transplant setting
• Relapse free survival (RFS-ctDNA) for nivolumab treated patients
• Proportion of patients who are able to convert from ctDNA positive to ctDNA negative after nivolumab treatment
• To validate NeoLabs assay platform by comparing the results to Clonoseq platform.

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