This pilot study has been designed to investigate the safety of pembrolizumab treatment for disease relapse following allogeneic stem cell transplant (alloSCT). Pembrolizumab will be administered at a fixed dose of 200 mg IV every 3 weeks. Approximately 12-26 patients with relapsed MDS, AML, or mature B cell (B-NHL, cHL) malignancies that have relapsed following alloSCT will be enrolled on this trial. Pembrolizumab treatment will be administered for up to 24 months, provided that neither disease progression, nor development of a dose-limiting toxicity (DLT), has occurred. Adverse events will be monitored every three weeks throughout the trial and graded in severity according to the guidelines outlined in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. This trial will be conducted in accordance with Good Clinical Practices.

Inclusion Criteria:

• Male or female subjects with AML, MDS or mature B cell lymphomas that have relapsed following matched-related donor (MRD) or matched unrelated donor (MUD) (HLA-A -B -C -DR -DQ) alloSCT are eligible for enrollment

  1. Signed written informed consent

     1. Subjects must have signed and dated an IRB-approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
     2. Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.

  2. Target population

     1. Subjects must be ≥ 18 years of age.

     2. Subjects must have an ECOG performance status of 0-1 (Appendix).

     3. Subjects have undergone alloSCT > 90 days prior to enrollment from a matched-related donor (MRD), matched-unrelated donor (MUD), cord blood donor, or haplo-identical and cord blood donor.

     4. There must be histological confirmation of relapse after alloSCT of any of the following diseases: any mature B cell lymphoma (cHL or NHL), AML or MDS.

     5. Subjects must be off of all immunosuppressive medications for a minimum of 2 weeks with the exception of physiologic doses of corticosteroids.

     6. Subjects with B cell lymphoma must have measurable disease, defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with CT scan. Minimum measurement must be > 15 mm in the longest diameter and > 10 mm in the short axis.

     7. Subjects must not have had any prior investigational agents or devices within 4 weeks of beginning study drug

     8. Subjects must have no prior history of VOD

     9. Subjects must demonstrate adequate organ function as defined below. All screening labs should be performed within 10 days of treatment initiation.

        Hematological Absolute neutrophil count (ANC) ≥ 500 /mcL Platelets ≥ 20,000 /mcL Hemoglobin ≥ 8 g/dL (RBC transfusions are OK)

        Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤ 1.5 X upper limit of normal (ULN) or

        • 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN

        Hepatic Serum total bilirubin ≤ 1.5 X ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5X ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN Albumin ≥ 2.0 mg/dL

        Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy, in which case, the PT/INR should be within therapeutic range for intended use. Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy, in which case, the PTT should be within therapeutic range for intended use.

        *Creatinine clearance should be calculated per institutional standard.

     10. Female subjects of childbearing potential should have a negative urine or serum pregnancy test (β-hCG) within 72 hours prior to receiving the first dose of study medication.

     11. Female subjects with childbearing potential should be willing to use 2 methods of contraception, be surgically sterile, or abstain from heterosexual activity throughout the course of the study, until 120 days after the final dose of study medication. Subjects with childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Abstinence is acceptable if this is the established and preferred contraceptive method for the subject.

     12. Male subjects should agree to use an adequate method of contraception starting with the first dose of study medication until 120 days after the final dose of study medicine. Abstinence is acceptable if this is the established and preferred contraceptive method for the subject.

Exclusion Criteria:

• 1. Target disease exclusions

  1. Subjects must not have known central nervous system involvement by disease (parenchymal, meningeal or cerebrospinal fluid) 2. Medical history, concurrent diseases, and prior treatments
  1. Subjects must not have a history of any positive test for hepatitis B or hepatitis C indicating active disease or previous exposure.
  2. Subjects must not have a history of human immunodeficiency virus (HIV) infection.
  3. Subjects must not be receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to the first dose of study medication. The use of physiologic doses of corticosteroids is acceptable.
  4. Subjects must not be concurrently receiving disease-modifying therapy in another therapeutic investigational study.
  5. Subjects must not have received a prior monoclonal antibody within 4 weeks prior to the first dose of study medication, and must have recovered (≤ grade 1) from adverse events related to any anti-cancer agent administered > 4 weeks previous to the first dose of study medication.
  6. Subjects must not have received chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of study medication, and must have recovered (≤ grade 1) from adverse events related to a previously administered agent.
  7. Subjects must not have received a donor lymphocyte infusion (DLI) within 8 weeks prior to the first dose of study medication.
  8. Subjects must not have a history of severe (grade 3-4) acute GVHD, and/or current > grade 1 acute GHVD. Subjects must not have a history of chronic GVHD (whether limited or extensive stage).
  9. Subjects must not have 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.
  10. Subjects must not have a known history of congestive heart failure, unstable angina pectoris, or cardiac arrhythmia (with the exception of chronic and rate-controlled atrial fibrillation).
  11. Subjects must not have a history of other serious underlying medical or psychiatric condition that, in the opinion of the investigator, would impair the ability to receive, tolerate and or comply with the planned treatment and follow-up.
  12. Subjects must not have a history of a known secondary primary malignancy that is not in remission and/or that requires active therapy. Exceptions include non-melanoma skin cancers and in situ cervical cancer that has undergone curative-intent local therapy.
  13. Subjects must not have a known active infection requiring intravenous antibiotic therapy.
  14. Subjects must not have a history of (non-infectious) pneumonitis that required steroid treatment, evidence of interstitial lung disease, or active, non-infectious pneumonitis. Subjects must not have active, non-infectious colitis.
  15. Subjects must not be pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the final dose of study medication.
  16. Subjects must not have received a live vaccine within 30 days prior to the first dose of study medication.
  17. Subjects must not be or have an immediate family member (spouse, parent, legal guardian, sibling or child) who is an investigational site sponsor or staff directly involved with the trial, unless IRB approval is granted previously.