INCLUSION CRITERIA

• Subject is ≥18 years of age at the time of signing the informed consent form (ICF).
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• All subjects must have documented diagnosis of MM and be eligible for commercial CAR-T therapy with either cilta-cel or ide-cel.
• All subjects must have ≥2 prior lines of multiple myeloma directed therapy, as determined by their treating clinician
• All patients must have ECOG Performance Status ≤ 2.
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy tests (minimum sensitivity 25 IU/L or equivalent units of hCG), at screening (10-14 days prior to start of study drug); another within 24 hours prior to the start of study drug.
• Women must not be breastfeeding
• WOCBP must agree to follow instructions for method(s) of contraception for 1 month (4 weeks) before the start of treatment with study drugs, for the duration of treatment with study drugs, and for a total of 1 month (4 weeks) after completion of iberdomide.
• Males who are sexually active with WOCBP must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking Iberdomide (CC-220) and for up to 90 days after discontinuing Iberdomide (CC-220), even if they have undergone a successful vasectomy. Male patients must not donate sperm.
• Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, they must still undergo pregnancy testing as described in this section.
• All subjects must agree not to share study medication.

EXCLUSION CRITERIA

• Subjects with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), primary amyloidosis (no active multiple myeloma), Waldenström's macroglobulinemia, or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

• Subjects with active plasma cell leukemia (defined as either 20% of peripheral blood white blood cell count comprised of plasma/CD138+ cells or an absolute plasma cell count of 2 x 109/L)

• Subjects with active Central Nervous System involvement with multiple myeloma

• Subjects with active multiple myeloma that cannot be safely managed with single-agent iberdomide for the duration of the priming period, per the discretion of the treating physician or PI

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form

• Any serious concurrent medical conditions that may make the patient non-evaluable or put the patient's safety at risk, per the discretion of the treating physician or PI

• Subjects with an active infection that requires parenteral anti-infective treatment within 7 days

• Unable to tolerate thromboembolic prophylaxis while on iberdomide

• Severe hypersensitivity reaction to prior IMiD (thalidomide, lenalidomide or pomalidomide)

• Grade > 2 peripheral neuropathy (per NCI CTCAE v5.0)

• Patients with a positive PCR test for hepatitis B virus or hepatitis C virus indicating active infection. Patients with positive serologic testing indicating exposure will need confirmatory testing by PCR.

• Patients with detectable HIV viral load or known acquired immunodeficiency syndrome (AIDS).

• Prior or concurrent malignancy, except for the following:

  • Adequately treated basal cell or squamous cell skin cancer or in-situ carcinoma.
  • Non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured.
  • Localized prostate cancer (N0M0):
  • with a Gleason score of ≤6, treated within the last 24 months or untreated and under surveillance,
  • with a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence; or
  • any history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence per the discretion of the treating physician or PI
  • Non-invasive cervical cancer treated within the last 24 months that is considered completely cured.
  • Breast cancer: adequately treated lobular carcinoma in situ, or ductal carcinoma in situ, or history of localized breast cancer and receiving anti-hormonal agents and considered to have a very low risk of recurrence.
  • Any other cancer from which the subject has been disease free for > 3 years prior to study entry, or considered cured with minimal risk of disease recurrence.

• Prior treatment with Iberdomide (CC-220) within 6 months prior to enrollment

• Prior allogeneic stem cell transplant except subjects who have completed the stem cell transplant > 12 months prior to first dose of study drug, have no history of graft versus host disease, and are not on systemic immunosuppressive therapy

• Major cardiac surgery within 8 weeks prior to the first dose of study drug; all other major surgery within 4 weeks prior to the first dose of study drug.

• Subjects with following physical and laboratory test findings:

  • Absolute neutrophil count < 1 x 109/L without growth factor support within 1 week, or absolute neutrophil count < 0.5 x 109/L for patients with documented Duffy-null blood typing
  • Platelets < 50 x 109/L without transfusion support within 1 week
  • Creatinine clearance < 30 ml/min according to the Cockroft-Gault formula:

• Female CrCl = [(140 - age in years) x weight in kg x 0.85] / [72 x serum creatinine in mg/dl]

• Male CrCl = [(140 - age in years) x weight in kg x 1.00] / [72 x serum creatinine in mg/dl]

  • Total bilirubin ≥ 2 x ULN (≥ 3 x ULN if documented Gilbert's syndrome)
  • AST or ALT ≥ 3x ULN
  • Corrected serum calcium > 13.5 mg/dL

• Are also excluded:

  • Prisoners or subjects who are involuntarily incarcerated
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness