A Study of Pembrolizumab (MK-3475) in Combination With Standard of Care Treatments in Participants With Multiple Myeloma (MK-3475-023/KEYNOTE-023)

Inclusion Criteria:

All Participants:

* Confirmed diagnosis of multiple myeloma (MM)
* MM with measurable disease
* Archival or newly obtained bone marrow material available. In addition, for participants in the United States (US) and Canada, able to provide newly obtained bone marrow aspirate for biomarker analysis.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate organ function
* Female participants of childbearing potential must 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 treatment
* Male participants must agree to use a latex condom during sexual contact with females of childbearing potential even if they have had a successful vasectomy starting with the first dose of study treatment through 120 days after the last dose of study treatment
* Able to swallow capsules and able to take or tolerate oral medications on a continuous basis

Dose Determination Arm, Dose Confirmation Arm and Cohort 1 Participants:

* Must have undergone prior treatment with ≥ 2 treatment lines of anti-myeloma therapy and must have failed their last line of treatment
* Prior anti-myeloma treatments must have included an immunomodulatory (IMiD) treatment (lenalidomide, pomalidomide or thalidomide) AND proteasome inhibitor (bortezomib or carfilzomib) alone or in combination and participant must have failed therapy with an IMiD OR proteasome inhibitor
* Must agree to follow the regional requirements for lenalidomide counseling, pregnancy testing, and birth control; willing and able to comply with the regional requirements (for example, periodic pregnancy tests and safety labs)

Cohort 2 Participants:

* MM with relapsing or refractory disease at study entry
* Received prior treatment with 1 to 3 lines for MM
* Achieved a partial response to at least one prior regimen (defined as ≥50% decrease in tumor burden)
* Left ventricular ejection fraction of at least 40%

Exclusion Criteria:

All Participants:

* Currently participating in and receiving study therapy or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment
* History of repeated infections; primary amyloidosis; hyperviscosity; plasma cell leukemia; polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome or Waldenström's macroglobulinemia
* Diagnosis of immunosuppressive disorder or on any other immunosuppressive therapy within 7 days prior to the first dose of study treatment
* Received a prior monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline) from a baseline AE or a Grade 1 AE associated with agents administered more than 4 weeks earlier
* Prior anti-MM therapy (including dexamethasone), targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from AEs due to a previously administered agent
* An additional malignancy that is progressing or requires active treatment within the last 5 years
* Active autoimmune disease or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
* Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
* Active infection requiring intravenous systemic therapy
* Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
* Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 120 days after the last dose of study treatment
* Prior therapy with an anti-programmed cell death (PD)-1, anti-PD ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137 antibody, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody
* Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection
* Clinically significant coagulopathy
* Has had or is planning for allogeneic stem cell transplant
* Autologous stem cell transplant within 12 weeks before the first infusion
* History of Grade 4 rash associated with thalidomide treatment
* Known hypersensitivity to thalidomide, lenalidomide or pomalidomide
* Received a live vaccine within 30 days of planned start of study treatment

Dose Determination Arm, Dose Confirmation Arm and Cohort 1 Participants:

* Clinically active central nervous system (CNS) involvement
* Known gastrointestinal disease that may significantly alter the absorption of lenalidomide
* Unable or unwilling to undergo antithrombotic prophylactic treatment
* Known symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia

Cohort 2 Participants:

* Smoldering MM (SMM), monoclonal gammopathy of undetermined significance (MGUS), plasma cell leukemia or Waldenström's macroglobulinemia
* Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to the first dose of study treatment
* Myocardial infarction within 4 months prior to randomization, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless participant has a pacemaker.
* Known history of allergy to CAPTISOL® (a cyclodextrin derivative used to solubilize carfilzomib)
* Hypersensitivity to carfilzomib, bortezomib, boron, or mannitol
* Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to pre-existing pulmonary or cardiac impairment
* Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to the first dose of study treatment
* Pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to the first dose of study treatment