Multiple Myeloma Clinical Trials

• Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.

• Patient must be able to understand the study procedures.

• Patient has given voluntary written informed consent before performance of any studyrelated procedure non part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.

• Newly diagnosed multiple myeloma patient who requires start active treatment according to the 2014 IMWG criteria, namely clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events: evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: Hypercalcaemia, Anaemia, Renal Insufficiency, or Bone lesions (one or more osteolytic lesions on skeletal radiography, CT, or PET-CT), and any one or more of the following biomarkers: clonal BMPC% ≥60%, i/u free light ratio ≥100 or \> 1 focal lesions on MRI or PET/CT) \[Lancet Oncol. 2014;15(12): e538-e548\].

• Patient must have a measurable secretory disease defined as either serum monoclonal protein of ≥ 0,5 g/dl or urine monoclonal (light chain) protein ≥ 200 mg/24 h. For patients whose disease is only measurable by serum FLC, the involved FLC should be ≥ 10mg/dL (100 mg/L), with an abnormal serum FLC ratio.

• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

• Patient must be ≤ 65 years of age.

• Patient must have adequate organ function, defined as follows:

‣ Absolute neutrophil count (ANC) ≥1.0 X 109/L without G-CSF use in the prior 7 days

⁃ Hemoglobin ≥8.0 g/dL (prior red blood cell (RBC) transfusion or recombinant human erythropoietin use is permitted)

⁃ Platelets ≥ 75 x 109/L in participants in whom \<50% of bone marrow nucleated cells are plasma cells and ≥ 50×109/L in participants in whom ≥50% of bone marrow nucleated cells are plasma cells (without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test).

⁃ Calcium Corrected serum calcium ≤13.5 mg/dL (≤3.4 mmol/L); or free ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L).

⁃ Total bilirubin ≤2 X ULN

⁃ ALT ≤2.5 X ULN

⁃ AST ≤2.5 X ULN

⁃ Renal: eGFRa: ≥40 mL/min/ 1.73 m2

⁃ Cardiac: LVEF (echo) ≥ 50%

• Female patient: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female patient is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:

‣ Is not a woman of childbearing potential (WOCBP), i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy OR

⁃ Is a WOCBP and

• She understands the potential teratogenic risk to the unborn child

∙ She understands the need for effective contraception as stated in the protocol, without interruption, 28 days before starting study treatment, throughout the entire duration of study treatment, during dose interruptions and for at least 28 days after the last dose of study treatment.

∙ She understands and agrees to inform the Investigator if a change or stop of method of contraception is needed.

∙ She must be capable of complying with effective contraceptive measures.

∙ She is informed and understands the potential consequences of pregnancy and the need to notify her study doctor immediately if there is a risk of pregnancy.

∙ She understands the need to commence study treatment as soon as it is dispensed following a negative pregnancy test.

∙ She understands and accepts the need to undergo pregnancy testing based on the frequency outlined in this plan and in the Informed Consent.

∙ She acknowledges she understands the hazards iberdomide or lenalidomide can cause to an unborn fetus and the necessary precautions associated with the use of study drugs.

• The Investigator must ensure that a WOCBP: i) Complies with the conditions of the pregnancy prevention plan, including confirmation that she has an adequate level of understanding. ii) Acknowledges the aforementioned requirements.

• A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study drug.

• Nonchildbearing potential is defined as follows (by other than medical reasons):

⁃ Has not achieved menarche at some point.

⁃ Has undergone a hysterectomy or bilateral oophorectomy.

⁃ Has 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).

⁃ Male patient: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

⁃ Male patient is eligible to participate if he agrees to the following from the time of first dose of study until 6 months after the last dose of iberdomide or lenalidomide to allow for clearance of any altered sperm:

‣ Understand the potential teratogenic risk if engaged in sexual activity with a pregnant female or a WOCBP.

‣ Understand the need for the use of a condom even if he has had a vasectomy, if engaged in sexual activity with a pregnant female or a FCBP

‣ Understand the potential teratogenic risk, so the subject should not donate semen or sperm.. Understand that the effects on fertility are currently unknown, therefore all family planning options and/or alternatives should be thoroughly discussed with the study doctor prior to receiving iberdomide.

⁃ All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 must be ≤ Grade 1 at the time of enrolment except for alopecia.