Pembrolizumab and Radiation Therapy in Patients With Relapsed or Refractory Multiple Myeloma

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