• Documented informed consent of the participant and/or legally authorized representative

‣ Assent, when appropriate, will be obtained per institutional guidelines

• Agreement to allow the use of archival tissue from diagnostic tumor biopsies

‣ If unavailable, exceptions may be granted with study principal investigator (PI) approval

• Eastern Cooperative Oncology Group (ECOG) =\< 2

• Life expectancy \> 3 months

• Diagnosis of multiple myeloma with measurable disease as defined by:

‣ M-protein quantities \>= 0.5 g/dL by serum protein electrophoresis (sPEP) or

⁃ \>= 200 mg/24 hour urine collection by urine protein electrophoresis (uPEP) or

⁃ Serum free light chain (FLC) \> 10.0 mg/dL involved light chain and an abnormal kappa/lambda ration in subjects without detectable serum or urine M-protein or

⁃ For subjects with immunoglobulin class A (IgA) myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA level \>= 0.50 g/dL

• Relapsed or refractory to at least 1 prior line of therapy, including both a proteasome inhibitor and an immunomodulatory drug, and for whom transplant is not recommended. Participants may opt for a delayed transplant at a later time, if appropriate

• Fully recovered from the acute toxic effects (except alopecia) to =\< grade 2 to prior anti-cancer therapy

• Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)

‣ NOTE: Screening ANC should be independent of granulocyte- and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G-CSF for at least 2 weeks

• Platelets \>= 75.0 x 10\^9/L (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)

‣ NOTE: Screening platelet count should be independent of platelet transfusions for at least 2 weeks

• Hemoglobin \>= 8.0 g/dL (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)

‣ NOTE: Transfusion support is allowed

• Total bilirubin =\< 2 X upper limit of normal (ULN) (unless has Gilbert's disease) (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)

• Aspartate aminotransferase (AST) =\< 3.5 x ULN (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)

• Alanine aminotransferase (ALT) =\< 3.5 x ULN (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)

• Alkaline phosphatase \< 5 x ULN (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)

• Creatinine clearance of \>= 30 mL/min per 24 hour urine test (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

‣ If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

• Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 4 weeks after the last dose of protocol therapy

‣ Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)