The following criteria is provided for health care professionals.

Inclusion Criteria:

• International Staging System (ISS) stage I-III multiple myeloma that has progressive, relapsed, or refractory disease
• Able to give informed consent
• Eastern Cooperative Oncology Group (ECOG) 0-1
• Relapsed and/or refractory myeloma; there is no minimum or maximum number of previous therapies that a patient may have received previously before being put on the current trial
• ≥ 1 osseous and/or extra-osseous lesion that can be radiated
• Candidate for pembrolizumab (as determined by physician, and adequate organ function)
• Candidate for radiotherapy (as determined by treatment physician); these patients can have symptomatic disease and/or asymptomatic disease; a minimum of one site of radiation is required to any osseous and/or any extra-osseous disease; radiation to any bony parts of the head and neck, skull, spine, ribs, and/or extremities are allowed; radiation to any bony part for documented lytic disease is allowed; radiation to any soft tissue plasmacytoma (including osseous and extra-osseous plasmacytoma) is allowed; the only exclusion criteria for radiation, is central nervous system (CNS) metastases
• Measurable myeloma disease (urine protein > 200 mg in 24 hours [hr] urine collection, serum free light chain ratio > 100 with an abnormal k/l ratio, serum M protein > 0.5 g/dl); 12 of the 24 patients do not have to have measurable disease
• Negative urine pregnancy test within 2 weeks for female subjects; female subjects of childbearing potential should have a negative urine or serum pregnancy 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 should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
  • Male subjects should agree to use an adequate method of 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 life style and preferred contraception for the patient

Exclusion Criteria:

• Previous anti-programmed cell death protein 1 (PD1) or anti-PD-L1
• Solitary plasmacytoma
• Smoldering (asymptomatic) multiple myeloma
• 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 diagnosis of immunodeficiency
• Known history of active TB (Bacillus tuberculosis)
• Hypersensitivity to pembrolizumab or any of its recipients
• 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)
• Has 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)
• Known history of, or any evidence of active, non-infectious pneumonitis
• Active infection requiring systemic therapy
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
• Has received a live vaccine within 30 days of planned start of study therapy; NOTE: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
• Patients requiring radiation for CNS diseases are excluded (CNS defined as brain soft tissue/intra parenchymal metastases within the gray and white matter of the brain and/or for cerebrospinal fluid [CSF] disseminated disease, including leptomeningeal carcinomatous disease)
• Has a history of allogeneic stem cell transplantation