The following criteria is provided for health care professionals.

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

• Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)
• For Cohorts 1 and 2 only, participant has measurable disease, defined as:
  • M-protein (serum protein electrophoresis [sPEP] or urine protein electrophoresis [uPEP]): sPEP ≥ 0.5 g/dL or uPEP ≥ 200 mg/24 hours and/or
  • Light chain MM without measurable disease in the serum or urine: Serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio

Subjects with one of the following cohort specific requirements:

• Cohort 1 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens:
  • Subject must have received at least 3 prior anti-myeloma treatment regimens. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen
  • Subject must have undergone at least 2 consecutive cycles of treatment for each regimen, unless PD was the best response to the regimen
  • Subject must have received prior treatment with a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody
  • Subject has evidence of PD on or within 60 days of the most recent prior treatment regimen
  • Subject achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen
• Cohort 2 subjects with 1 prior anti-myeloma treatment regimen:
  • Subject must have received only 1 prior anti-myeloma treatment regimen. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen
  • Subject must have the following HR factors:
  • Early relapse defined as:
    • Cohort 2a: PD < 18 months since date of start of initial therapy. Initial therapy must contain induction, ASCT (single or tandem) and lenalidomide containing maintenance.
    • Cohort 2b: PD < 18 months since date of start or initial therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone
    • Cohort 2c: Subject must have received minimum 3 cycles of induction therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone. Subjects must have had ASCT (single or tandem AND < VGPR (excluding PD) at first assessment between 70 to 110 days after last ASCT, with initial therapy without consolidation and maintenance.
• Cohort 3 participants with newly diagnosed MM (NDMM) who received only induction and ASCT, without subsequent consolidation or maintenance Cohort 3
• • • Must have received 4 to 6 cycles of induction therapy which must contain at minimum, a proteasome inhibitor and an immunomodulatory agent and must have had single ASCT within 6 months prior to consent
    • Must have achieved documented PR or VGPR at first post-ASCT assessment approximately 100 days after ASCT and this response must be maintained at screening
    • Per Investigator's assessment, subject must be a candidate for single-agent lenalidomide maintenance
• Subject must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Subject must have recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 neuropathy

Exclusion Criteria:

• The presence of any of the following will exclude a subject from enrollment:
  • Subject used any investigational agents within 14 days prior to leukapheresis or, for Cohort 3, within 14 days prior to consent
  • Subject received any of the following within the last 14 days prior to leukapheresis or, for Cohort 3, within 14 days prior to consent:
    • Plasmapheresis
    • Major surgery (as defined by the investigator)
    • Radiation therapy other than local therapy for myeloma associated bone lesions
    • Use of any systemic anti-myeloma drug therapy
  • Subject with known central nervous system involvement with myeloma
  • Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation
  • History or presence of clinically relevant central nervous system (CNS) pathology
  • Subject with active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, or clinically significant amyloidosis
  • Inadequate organ function Subject with a history of Class III or IV congestive heart failure (CHF) or severe nonischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months prior to starting study treatment
  • Ongoing treatment with chronic immunosuppressants
  • Previous history of an allogeneic hematopoietic stem cell transplantation or treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or BCMA targeted therapy
  • Subject has received ASCT within 12 weeks prior to leukapheresis
  • Subject has history of primary immunodeficiency
  • Subject is positive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B or active hepatitis A or C
  • Subject has uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment
  • Subject with prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years
  • Pregnant or lactating women
  • Subject with known hypersensitivity to any component of bb2121 product, cyclophosphamide, fludarabine, and/or tocilizumab
  • Prior history of deep venous thrombosis (DVT) or pulmonary embolus (PE) within 6 months prior to consent (For Cohort 3)