Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Diffuse Large B-cell Lymphoma or Grade 3b Follicular Lymphoma

Inclusion Criteria

• Previously untreated diffuse large B-cell lymphoma or grade 3B follicular lymphoma (of any stage); subjects must be planned to receive full course (6 cycles) of RCHOP chemoimmunotherapy as per clinical standard of care; patients may have de novo DLBCL, and /or any of the following:
• Composite lymphomas, which include both diffuse DLBCL and another histology (most commonly follicular lymphoma) in the same lymph node
• Transformed lymphoma with DLBCL histology, as long as the patient has not received prior therapy for lymphoma
• Discordant presentations, such as DLBCL in a lymph node and low-grade lymphoma such as follicular lymphoma in the bone marrow
• Be willing and able to provide written informed consent/assent for the trial
• Have measurable nodal disease, including at least 1 disease site measuring 1.5 cm in longest dimension on computed tomography (CT) or fludeoxyglucose (FDG)-positron emission tomography (PET)
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale (PS)
• Absolute neutrophil count (ANC) >= 1, 500/mcL except in cases of marrow infiltration by lymphoma
• Platelets >= 100, 000/mcL except in cases of marrow infiltration by lymphoma
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L except in cases of marrow infiltration by lymphoma
• Serum creatinine = = 60 ml/min for subject with creatinine levels > 1.5 X institutional ULN (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl])
• Serum total bilirubin = 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) = 1 year
• Male subjects should agree to use an adequate method of barrier contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

Exclusion Criteria

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study drug or using an investigation device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
• No active autoimmune disease that has required systemic treatment in 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
• Has history of non-infectious pneumonitis that required steroids or current pneumonitis
• Has an active infection requiring intravenous antibiotic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation