Upfront Chimeric Antigen Receptor T-Cell to Upgrade Response in Multiple Myeloma

Inclusion Criteria

• Age greater than or equal to 18.00 years
• Patients must meet the criteria for symptomatic MM requiring therapy (Appendix A) prior to initiating initial systemic anti-myeloma treatment.
• Patients must have received initial systemic anti- myeloma therapy consisting of induction therapy and consolidation with high-dose melphalan (>140 mg/m^2 ) followed by an auto HCT (minimum cell dose of 2x10^6 CD34+ cells/kg (actual body weight) within 12 months from initiation of systemic anti-myeloma therapy.
• Patient must have additional stored stem cells greater than or equal to 2x10^6 CD34+ cells per kg actual body weight.
• Patients must be less than or equal to 12 months after autologous HCT at the time of enrollment.
• Patients must have initiated maintenance therapy with lenalidomide-based regimen within 6 months after the auto HCT and have received at least 3 months of maintenance prior to enrollment.
• Patients must have tolerated a minimum dose of lenalidomide 5 mg/day for 21 days of a 28-day cycle for greater than 2 cycles without having to stop due to toxicities.
• Patients must have a VGPR or less (Section 3.1) in reference to time time of initiation of initial systemic anti-myeloma therapy at study enrollment.
• Patients must have Karnofsky performance greater than or equal to 70.
• Patients must have recovered to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding Grade 2 neuropathy.
• Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3 without filgrastim use in the prior 14 days.
• Platelet count greater than 100, 000/mm^3 (without platelet transfusion in the previous 7 days or thrombopoietin mimetics in the previous 28 days).
• Hemoglobin greater than 9 g/dL (without red blood cell transfusion in the previous 7 days).
• Creatinine Clearance (CrCl) greater than or equal to 60 mL/min, measured or estimated by Cockcroft-Gault equation.
• Corrected serum calcium less than or equal to 13.5 mg/dL.
• Oxygen saturation greater than 92% on room air.
• Hepatic Function: a. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x upper limit of normal (ULN) b. Serum total bilirubin less than or equal to 2 x ULN. Patients who have been diagnosed with Gilbert's disease are permitted to exceed the defined bilirubin value of 2 x ULN
• International ratio (INR) or partial thromboplastin time (PTT) less than 1.5 x ULN
• Cardiac Function: left ventricular ejection fraction greater than 45% by echocardiogram or MUGA.
• Patients must be willing and able to adhere to the study visit schedule and other protocol requirements including regulatory requirement of a 15 year follow up using the CIBMTR long term follow up mechanism.
• Female patients of childbearing potential (FCBP1 ) must: a. Have a negative serum pregnancy test with a sensitivity of at least 50 mIU/mL prior to enrollment b. Agree to use, and be able to comply with, TWO acceptable methods of birth control (Appendix C), one highly effective method and one additional effective (barrier) method AT THE SAME TIME, from screening through at least 1 year following bb2121 infusion or 4 weeks following discontinuation of lenalidomide, whichever is later. c. Agree to abstain from breastfeeding from screening through at least 1 year following bb2121 infusion or 4 weeks following discontinuation of lenalidomide, whichever is later.
• Male patients must: a. Agree to use a condom during sexual contact with a pregnant female or a FCBP, even if he has undergone a successful vasectomy, from screening through at least 1 year following bb2121 infusion or 4 weeks following discontinuation of lenalidomide whichever is later b. Must not donate sperm from screening through at least 1 year following bb2121 infusion or 4 weeks following discontinuation of lenalidomide whichever is later.

Exclusion Criteria

• Patients with a prior allogeneic hematopoieti