Inclusion Criteria:

• Age ≥ 18 years old at time of study entry (consent) or adult male or female (For Nebraska, age of consent is ≥19 years old)
• The subject is willing and able to provide informed consent to and abide by the protocol.
• Subject must understand and voluntarily sign an informed consent form prior to any study-related assessments/procedures being conducted.
• Subjects must have a documented history of a diagnosis of active Multiple Myeloma (MM)
  • Measurable disease documented at time of diagnosis (prior to induction and ASCT) as defined as: i. M-protein (serum and/or urine protein electrophoresis (SPEP or UPEP)): SPEP ≥ 0.5 g/dL or UPEP ≥ 200 mg/24 hours and/or ii. Light chain MM without measurable disease in the serum or urine: serum immunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa-lambda free light chain ratio
• Prior MM therapy
  • Initiation of induction therapy within 12 months of registration
  • No prior progression after initial therapy. Subjects whose induction therapy was changed due to suboptimal response or intolerance remain eligible, provided they do not meet criteria for progression as per the 2016 IMWG Response Criteria. In addition, no more than two regimens will be allowed excluding dexamethasone alone.
  • No prior allogeneic hematopoietic stem cell transplant or solid organ transplant
• Undergone ASCT with high-dose melphalan (140-200 mg/m2) and in a documented continued partial response or better (as per IMWG criteria) at day 80-110 post-ASCT.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months) and must:
  • Have two negative serum or urine pregnancy tests as verified by the Investigator prior to starting study treatment. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact.
  • Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with two forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting investigational product, during the study treatment (including dose interruptions), and for at least 28 days after the last dose of iberdomide.
• Male subjects must:
  • Male subjects must practice complete abstinence (True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence [e.g. calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal are not acceptable methods of contraception) or agree to use a condom during sexual contact with a pregnant female or a FCBP while taking iberdomide, during dose interruptions and for at least 90 days following the last dose of iberdomide even if he has undergone a successful vasectomy.
• Males must agree to refrain from donating sperm while on study treatment, during dose interruptions and for at least 90 days following last dose of study treatment.
• All subjects must agree to refrain from donating blood while on study treatment, during dose interruptions and for at least 28 days following the last dose of study treatment.
• All male and female subjects must follow all requirements defined in the Pregnancy Prevention Program.

Exclusion Criteria:

• Participation in another clinical study with an investigational product during the last 28 days prior to registration
• Subject is a female who is pregnant, nursing or breastfeeding, or who intends to become pregnant during the participation in the study
• Subject has any significant medical condition or psychiatric illness that would prevent the subject from participating in the study as judged by the treating physician
• Subject has MM disease progression (as defined by IMWG response criteria) following ASCT prior to registration
• Subject has nonsecretory MM
• Subject with plasma cell leukemia or light chain amyloidosis
• Any of the following laboratory abnormalities within 14 days of registration
  • Absolute neutrophil count (ANC) < 1,000/μL
  • Platelet count < 75,000/μL
  • Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)
  • Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST)or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) ≥ 2.0 x upper limit of normal (ULN)
  • Serum total bilirubin and alkaline phosphatase > 1.5 x ULN
  • Subjects with serious renal impairment ([CrCl] < 50 mL/min) or requiring dialysis would be excluded
• Subject with peripheral neuropathy ≥ Grade 2
• Subject with gastrointestinal disease that may significantly alter the absorption of iberdomide or inability to take medications by mouth
• Subject with a prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years prior to registration with the exception of the following noninvasive malignancies:
  • Basal cell carcinoma of the skin
  • Squamous cell carcinoma of the skin
  • Carcinoma in situ of the cervix
  • Carcinoma in situ of the breast
  • Incidental histological findings of prostate cancer such as T1a or T1b using the Tumor/Node/Metastasis (TNM) classification of malignant tumors or prostate cancer that is curative
• Subject has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, or pomalidomide
• Subject has received any of the following within 14 days prior to registration
  • Plasmapheresis
  • Major surgery (as defined by the Investigator)
  • Radiation therapy other than local therapy for MM associated bone lesions
  • Use of any systemic myeloma drug therapy
• Subject has any one of the following:
  • Clinically significant abnormal electrocardiogram (ECG) finding within 14 days of registration
  • Congestive heart failure (New York Heart Association Class III or IV)
  • Myocardial infarction within 12 months prior to registration
  • Unstable or poorly controlled angina pectoris, including the Prinzmetal variant of angina pectoris
• Subject has current or prior use of immunosuppressive medication within 14 days prior to registration. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical or local steroid injections (eg, intra-articular injection)
  • Systemic corticosteroids at physiologic doses that do not exceed 10 mg/day of prednisone or equivalent
  • Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication)
• Subject has taken a strong inhibitor or inducer of CYP3A4/5 including grapefruit, St. John's Wort or related products within two weeks prior to dosing and during the course of study
• Subject known to have tested positive for human immunodeficiency virus (HIV), chronic or active hepatitis B, or active hepatitis A or C (no testing will be done for the study, specifically)
• Prior therapy with iberdomide
• Subject is unable or unwilling to undergo protocol required thromboembolism prophylaxis