Bone Marrow Transplant Clinical Trials

• Participants must have had a confirmed diagnosis of symptomatic multiple myeloma according to according to IMWG diagnostic criteria.

• Measurable disease at the time of myeloma diagnosis Measurable disease is defined as measurable M protein in the serum (≥ 0.5g/dL) or urine (≥ 200 mg/24h) or serum free light chain assay (defined as dFLC ≥ 10 mg/dL \[≥ 100 mg/L\]; difference between involved and uninvolved free light chain) at the time of diagnosis. Participants with smoldering myeloma are not eligible until they have progressed to symptomatic myeloma. Participants with purely non-secretory MM at the time of diagnosis as measured by electrophoresis and immunofixation and the absence of Bence Jones proteins in the urine are not eligible.

• Age \>18 years.

• Patients who have already received transplant should have undergone autologous stem cell transplant with Melphalan 140 mg/m2 within 12 months of start of induction therapy of multiple myeloma and are within day +60-120 post-transplant. Patients who have not already received transplant must have begun induction therapy within 12 months prior to the planned date of transplant.

• Participants must not be refractory to lenalidomide

• Participants must not have progressive disease at any time prior to registration

• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.

• Have clinical laboratory values meeting the following criteria during the Screening Phase and also at start of administration of study treatment:

• \- Hemoglobin: ≥ 8 g/dL (≥ 4.96 mmol/L; without transfusion support or erythropoietin use within 7 days before the laboratory test)

• \- Platelets: ≥ 75×109/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)

• \- Absolute neutrophil count: ≥ 1.0×109/L (prior growth factor support is permitted but must be without support for 7 days for G-CSF or GM-CSF and for 14 days for pegylated GCSF before the laboratory test)

• \- AST and ALT: ≤2.5×ULN

⁃ Creatinine clearance: ≥30 mL/min based on Cockcroft Gault equation

⁃ Total bilirubin: ≤2.0×ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤1.5×ULN is required)

⁃ Serum calcium corrected for albumin: ≤14 mg/dL (≤3.5 mmol/L) or free ionized calcium ≤6.5 mg/dL

• (ALT=alanine aminotransferase; AST=aspartate aminotransferase; GCSF=granulocyte colony stimulating factor; GM-CSF=granulocyte-macrophage colony stimulating factor; RBC=red blood cell; ULN=upper limit of normal)

• A woman of childbearing potential must have a negative highly sensitive urine or serum (β human chorionic gonadotropin \[β hCG\]) pregnancy test at screening, again a negative serum test within 48 hours prior to the start of study treatment.

⁃ A woman must be:

∙ Not of childbearing potential, or

‣ Of childbearing potential and 1) Practicing true abstinence; or 2) Have a sole partner who is bilaterally vasectomized; or 3) Practicing 2 effective methods of contraception (at least 1 highly-effective, method of contraception (see 3 for methods of contraception allowed).

⁃ NOTE: Participant must agree to continue the above throughout the study and for 100 days after the last dose of study treatment.

⁃ NOTE: If a woman becomes of childbearing potential after start of the study the woman must comply with point (b) as described above. If a participant's reproductive status is questionable, additional evaluation should be considered.

⁃ NOTE: An interaction between hormonal contraception and talquetamab has not been formally studied. Therefore, it is unknown whether talquetamab may reduce the efficacy of the contraception method. If a woman is receiving talquetamab and is using hormonal contraceptives, an additional barrier method must be used.

⁃ NOTE: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.

⁃ A woman must agree not to donate eggs (ova, oocytes) or freeze for future use, for the purposes of assisted reproduction during the study and for 100 days after receiving the last dose of study treatment

⁃ A man must wear a condom (with spermicidal foam/gel/film/cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for a minimum of 100 days after receiving the last dose of study treatment. If a female partner is of childbearing potential, she must also be practicing a highly effective method of contraception (see Section 13.2, Appendix 2).

⁃ NOTE: If the male participant is vasectomized, he still must wear a condom (with foam/gel/film/cream/suppository), but his female partner is not required to use contraception.

⁃ A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 100 days after receiving the last dose of study treatment.

⁃ Must be willing and able to adhere to the lifestyle restrictions specified in this protocol ( Section 3.2), including to not donate blood or blood components during the study and for 100 days after the last dose of study drug). This includes complying with REMS program for lenalidomide. Per lenalidomide REMS program. In women of childbearing potential, pregnancy testing is needed weekly during the first month of treatment with lenalidomide, then monthly thereafter in females with regular menstrual cycles or every 2 weeks in females with irregular menstrual cycles.

⁃ Must sign an ICF (or their legally acceptable representative must sign) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.

⁃ Willingness to return to study site for follow-up