Pembrolizumab, Lenalidomide, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma Eligible for Stem Cell Transplant

Inclusion Criteria:

• Diagnosis and previously untreated active multiple myeloma by International MyelomaWorking Group (IMWG) diagnostic criteria for multiple myeloma

• Calculated creatinine clearance (using Cockcroft-Gault equation) >= 30 mL/min

• Absolute neutrophil count (ANC) >= 1000/mm^3

• Platelet count >= 75000/mm^3

• Hemoglobin >= 8.0 g/dL

• Total bilirubin =< 1.5 x upper limit of normal (ULN)

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN

• Prior therapy for the treatment of solitary plasmacytoma is permitted, but > 7 daysshould have elapsed from the last day of radiation

• NOTE: Prior therapy with clarithromycin, dehydroepiandrosterone (DHEA), anakinra,pamidronate, or zoledronic acid is permitted; any additional agents not listedmust be approved by the principal investigator

• Measurable disease of multiple myeloma as defined by at least ONE of the following:

• Serum monoclonal protein >= 1.0 g/dL

• > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis

• Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serumimmunoglobulin kappa to lambda free light chain ratio

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

• Provide written informed consent

• Negative pregnancy test done =< 7 days prior to registration, for women ofchildbearing potential only

• Willing to follow strict birth control measures as suggested by the study

• Female patients: If they are of childbearing potential, must agree to one of thefollowing:

• Practice 2 effective methods of contraception, at the same time, from thetime of signing the informed consent form through 90 days after the lastdose of study drug, AND must also adhere to the guidelines of anytreatment-specific pregnancy prevention program, if applicable, OR

• Agree to practice true abstinence when this is in line with the preferredand usual lifestyle of the subject (periodic abstinence [e.g., calendar,ovulation, symptothermal, post-ovulation methods] and withdrawal are notacceptable methods of contraception)

• Male patients: even if surgically sterilized (i.e., status post-vasectomy), mustagree to one of the following:

• Agree to practice effective barrier contraception during the entire studytreatment period and through 120 days after the last dose of study drug, OR

• Must also adhere to the guidelines of any treatment-specific pregnancyprevention program, if applicable, OR

• Agree to practice true abstinence when this is in line with the preferredand usual lifestyle of the subject (periodic abstinence [e.g., calendar,ovulation, symptothermal, post-ovulation methods] and withdrawal are notacceptable methods of contraception)

• Willing to return to enrolling institution for follow-up (during the active monitoringphase of the study)

• Willing to provide consent to Institutional Review Board (IRB) number (#) 521-93 andprovide research tissue and blood specimens

Exclusion Criteria:

• Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma

• Prior cytotoxic chemotherapy or corticosteroids for the treatment of multiple myeloma

• NOTE: Prior corticosteroid use for the treatment of non-malignant disorders ispermitted

• Diagnosed or treated for another malignancy =< 2 years before study enrollment orpreviously diagnosed with another malignancy and have any evidence of residualdisease.

• NOTE: Patients with nonmelanoma skin cancer or carcinoma in situ of any type arenot excluded if they have undergone complete resection

• Any of the following:

• Pregnant women

• Nursing women

• Men or women of childbearing potential who are unwilling to employ adequatecontraception

• Other co-morbidity which would interfere with patient's ability to participate intrial, e.g. uncontrolled infection, uncompensated heart or lung disease

• Other concurrent chemotherapy or any ancillary therapy considered investigational

• NOTE: Bisphosphonates are considered to be supportive care rather than therapy,and are thus allowed while on protocol treatment

• Peripheral neuropathy >= grade 3 on clinical examination or grade 2 with pain duringthe screening period

• Major surgery =< 14 days prior to study registration

• Radiotherapy =< 14 days prior to registration

• NOTE: If the involved field is small, 7 days will be considered a sufficientinterval between treatment and administration of study drugs

• Participation in any other clinical trials with other investigational agents notincluded in this trial, =< 21 days prior to registration

• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressivedrugs)

• NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologiccorticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.)is not considered a form of systemic treatment

• Has a history of (non-infectious) pneumonitis that required steroids or currentpneumonitis

• Active infection requiring systemic therapy

• History or current evidence of any condition, therapy, or laboratory abnormality thatmight confound the results of the trial, interfere with the subject's participationfor the full duration of the trial, or is not in the best interest of the subject toparticipate, in the opinion of the treating investigator

• Known psychiatric or substance abuse disorders that would interfere with cooperationwith the requirements of the trial

• Is pregnant or breastfeeding, or expecting to conceive or father children within theprojected duration of the trial, starting with the pre-screening or screening visitthrough 120 days after the last dose of trial treatment

• Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent

• Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

• Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) orhepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] isdetected)

• Received a live vaccine =< 30 days of planned start of study therapy