Pembrolizumab in Neoplasms or Lymphomas

Inclusion Criteria:

* Be willing and able to provide written informed consent for the trial.
* Histologically confirmed diagnosis of a histiocyte/dendritic cell neoplasm or relapsed/refractory aggressive lymphoma with at least one of the following features (with review required at a participating study center):

  * Diffuse large B cell lymphoma with Epstein-Barr virus (EBV) positive tumor cells (defined as positive EBV-encoded RNA in tumor cells)
  * Plasmablastic lymphoma
  * T cell/histiocyte rich DLBCL
  * EBV+ T cell lymphoma of any histology; note, patients with angioimmunoblastic T cell lymphoma will be eligible regardless of EBV status
  * Histiocytic sarcoma
  * Follicular dendritic cell sarcoma
  * Interdigitating dendritic cell sarcoma
* For patients with histiocytic sarcoma, interdigitating dendritic cell sarcoma, or follicular dendritic cell sarcoma only: disease that is not amenable to surgical resection and/or radiation therapy with curative intent.
* For lymphoma patients only: At least one prior systemic chemotherapy including an alkylating agent and anthracycline (unless contraindicated), and an anti-cluster of differentiate 20 (CD20) monoclonal antibody if the tumor is CD20+.
* For lymphoma patients only: Participants must have received and relapsed after autologous stem cell transplantation (ASCT), or be ineligible for ASCT (including on the basis of refractory disease), or have declined ASCT
* Age 18 years or older at the time of signing consent.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Karnofsky ≥70%, see Appendix A)
* Participants must have normal organ and marrow function as defined below:

  * absolute neutrophil count ≥ 1,000/microliter (mcL)
  * platelets ≥75,000/mcL (\> 30,000 if there is bone marrow involvement with lymphoma)
  * total bilirubin \< 1.5 times the institutional upper limit of normal (ULN) OR direct bilirubin \< the normal in subjects with total bilirubin \>1.5 times the ULN
  * Aspartate aminotransferase (AST)(SGOT)/ alanine aminotransferase (ALT) (SGPT) ≤2.5 × institutional ULN or \< 5 times ULN in patients with known hepatic involvement with lymphoma
  * albumin \> 2.5 mg/dl
  * creatinine \< 1.5 times the normal upper institutional limit OR creatinine clearance ≥60 mL/min/1.73 m2 in participants with creatinine levels \> 1.5 times the normal upper institutional limit
  * International normalized ratio (INR), activated partial thromboplastin time (aPTT) or prothrombin time (PT) \< 1.5 times the ULN unless subject is receiving anticoagulation therapy as long as PT or aPTT are within therapeutic range of intended use of anticoagulant
* Be willing to provide tissue from a newly obtained core needle or excisional biopsy. Newly-obtained is defined as a specimen obtained up to and including 90 days prior to treatment day 1. Subjects for whom newly obtained samples cannot be provided may be enrolled only with agreement by the overall PI.
* No prior allogeneic transplant unless all of the following apply:

  * At least 5 years from time of transplant
  * Absence of clinically significant graft-versus-host disease (GVHD)
  * Not on immune suppression
  * Approval of overall PI
* Not a candidate for potentially curative therapy at the time of enrollment
* Measurable disease per the Lugano criteria.
* Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
* Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 5.4.3 - Contraception for the course of the study through 120 days after the last dose of study medication.
* Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
* Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section 5.4.3- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
* Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
* The effects of pembrolizumab on the developing human fetus are unknown. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

Exclusion Criteria:

* Prior treatment with a PD-1, PD-L1 or PD-L2 inhibitor
* Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to study day 1 or has not recovered (i.e., \< grade 1 or at baseline) from adverse events due to a previously administered agent.
* Participants who have had chemotherapy, targeted small molecule therapy, or radiotherapy within 2 weeks prior to study day 1 (6 weeks for nitrosoureas or mitomycin C) or who has not recovered (i.e., \< grade 1 or at baseline) from adverse events due to previously administered agents. Note: subjects with \< grade 2 peripheral neuropathy are an exception to this criterion and may qualify for the study.
* Radiation therapy within 2 weeks of study treatment
* Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
* Has a known history of active tuberculosis
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* Has an active infection requiring systemic therapy.
* Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with the use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal her pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment or is taking chronic systemic steroids (in doses exceeding 10 mg daily of prednisone equivalent) within 7 days prior to the first dose of trial treatment. Note: Subjects with asthma or chronic obstructive pulmonary disease that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections are not excluded from the study.
* Has a history of non-infectious pneumonitis that required systemic corticosteroid treatment or has active pneumonitis.
* Known active central nervous system involvement 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 4 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. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
* Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
* Active hepatitis B (e.g., hepatitis B surface antigen reactive) or hepatitis C (e.g., hepatitis C virus RNA detectable).
* Human immunodeficiency virus (HIV 1/2).
* Is pregnant or breast-feeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit until 120 days after the last dose of trial treatment.
* Has received a live vaccine within 30 days of planned start of study therapy. (Note: seasonal influenza vaccines for injection are allowed as they are inactivated; however, intranasal influenza vaccines are live attenuated vaccines and are NOT allowed)
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab.
* Baseline pulse oximetry \<94% or requires oxygen supplementation of any kind
* If subject underwent major surgery they must have recovered adequately from the toxicity and/or complications from the procedure prior to starting therapy.
* Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia