Nivolumab for People with Newly Diagnosed Primary Central Nervous System Lymphoma following Completion of First-Line Chemotherapy

Inclusion Criteria

• BIOSPECIMEN AND DATA COLLECTION INCLUSION CRITERIA
• Histologically documented PCNSL with the ability to submit up to 20 unstained formalin-fixed, paraffin embedded (FFPE) slides from the initial tissue diagnosis prior to study registration or histologically confirmed lymphomatous involvement of the CSF and/or eye/vitreous
• Patients must be able to tolerate MRI/computed tomography (CT) scans with fludeoxyglucose F-18 ([18F FDG])
• Patients must be able to tolerate lumbar punctures and/or Ommaya taps
• ADDITIONAL INCLUSION CRITERIA FOR NIVOLUMAB MAINTENANCE ARM
• Persistent cfDNA in the CSF
• Participants must be able to understand and be willing to sign a written informed consent document
• Women and men who are at least 18 years of age on the day of consenting to the study
• Karnofsky performance status (KPS) >= 60
• Life expectancy of > 3 months (in the opinion of the investigator)
• Absolute neutrophil count (ANC) >= 0.75 x 10^9/L
• Platelets >= 75 x 10^9/L and no platelet transfusion within the past 21 days prior to study registration
• Hemoglobin (Hgb) >= 8 g/dL and no red blood cell (RBC) transfusion within the past 21 days prior to study registration
• International normalized ratio (INR) =< 1.5 and partial thromboplastin time (PTT) (aPTT) =< 1.5 times the upper limit of normal. Patients on anticoagulants should be managed according to MSK Standard Operating Procedures (SOPs)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 times the upper limit of normal
• Serum bilirubin =< 1.5 times the upper limit of normal; or total bilirubin =< 3 times the upper limit of normal with direct bilirubin within the normal range in patients with well documented Gilbert syndrome
• Serum creatinine =< 2 times the upper limit of normal
• Women of reproductive potential must agree to use highly effective methods of birth control during the period of therapy and for 5 months after the last dose of the study drug. Men who are sexually active must agree to use highly effective contraception during the period of therapy and for 7 months after the last dose
• Women of childbearing potential must have a negative plasma pregnancy test upon study entry

Exclusion Criteria

• BIOSPECIMEN AND DATA COLLECTION EXCLUSION CRITERIA
• Patients with recurrent/refractory PCNSL. Patients with stable disease as their best response to first-line chemotherapy will also come off study
• Patient with systemic, non-central nervous system (CNS) lymphoma metastatic to the CNS
• Patient is known to have human immunodeficiency virus (HIV) infection
• Patient is known to have a history of active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) as determined by serologic tests
• Patients who are planned to undergo consolidation with autologous hematopoietic cell transplantation (HSCT)
• ADDITIONAL EXCLUSION CRITERIA FOR NIVOLUMAB MAINTENANCE ARM
• Patient has undergone prior allogenic stem cell transplant
• Patients who are planned to undergo consolidation with autologous HSCT
• Any chemotherapy, external beam radiation therapy, or anticancer antibodies within 14 days of the first dose of study drug
• Patient is allergic to components of the study drug
• Patient is concurrently using other approved or investigational antineoplastic agents
• Previous or current treatment with an anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PDL2 agent
• Patient has an active concurrent malignancy requiring active therapy
• Patient is requiring escalating or chronic supraphysiologic doses of corticosteroids (> 8 mg dexamethasone daily) for control of disease at the time of registration
• Patient is using systemic immunosuppressant therapy including: cyclosporine A, tacrolimus, sirolimus, and other such medications, or chronic administration of > 5 mg/day of prednisone or the equivalent. Participants must be off immunosuppressant therapy for at least 28 days prior to the first dose of the study drug
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Known history of, or any evidence of active, non-infectious pneumonitis
• Patient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, uncontrolled congestive heart failure, uncontrolled hypertension, valvular disease, pericarditis, or myocardial infarction within 6 months of screening
• Peptic ulcer, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within past 6 months
• Patient is known to have an uncontrolled active systemic infection
• Patient has a life-threatening illness, medical condition, or organ system dysfunction that, in the opinion of the investigator, could compromise the subject’s safety or put the study outcomes at undue risk
• Women who are pregnant or nursing (lactating), where pregnancy is defined as a state of a female after conception until the termination of gestation, confirmed by a positive plasma human chorionic gonadotropin (hCG) laboratory test of > 5 mIU/mL
• The patient is unwell or unable to participate in all required study evaluations and procedures
• Participants who have received a live / attenuated vaccine within 30 days of first treatment