The following criteria is provided for health care professionals.
Abbreviated inclusion criteria:
- Diagnosis of r/r MM with measurable disease by at least one of the following:
- Serum M-protein ≥1.0 g/dL
- Urine M-protein ≥200 mg/24 hours
- Involved serum free light chain level ≥10 mg/dL, with an abnormal kappa-lambda ratio if the serum M-protein <1.0 g/dL and/or urine M-protein <200 mg/24 hours
- Regimens A and A1: MM relapsed or progressed after ≥3 prior approved therapies, including an IMiD, proteosome inhibitor, and anti-CD38 mAb
- Regimens B and B1: MM relapsed or progressed after ≥2 prior approved therapies, including an IMiD and PI
- Note: for all Regimens, prior BCMA CAR T-cell therapy and BCMA-targeted therapy (e.g., bi-specific engagers or antibody-drug conjugates) is allowed
Abbreviated exclusion criteria:
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2
- Evidence of insufficient hematologic function:
- ANC <1000/µL without growth factor support ≤7 days prior to measurement
- Platelet count <75,000/µL without platelet transfusion ≤72 hours prior to measurement
- Evidence of insufficient organ function
- CrCL <50 ml/min by Cockcroft-Gault or other institutional method
- T bilirubin >1.5x ULN, except for Gilbert's syndrome
- AST >3x ULN or ALT >3x ULN, unless directly due to underlying malignancy
- O2 sat <92% on room air
- Clinically significant cardiovascular disease:
- Myocardial infarction within 6 months of first treatment
- Unstable angina or CHF of NYHA Grade 2 or higher
- Cardiac EF <40%
- Subjects with prior central nervous system (CNS) involvement of MM must have completed effective treatment of their CNS disease at least 3 months prior to Day 1 with no evidence of disease clinically and at least stable findings on relevant CNS imaging
- Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions in the 2-year period leading up to study enrollment
- Currently receiving or likely to require systemic immunosuppressive therapy (e.g., prednisone >5 mg daily) for any reason during the treatment period, with the exception of corticosteroids.
- Clinically significant infections, including:
- HIV positive by serology
- HBV positive by serology or PCR
- HCV positive by serology or PCR
- Live vaccine <6 weeks prior to start of conditioning
- Receipt of an allograft organ transplant
- Prior allogeneic HSCT or allogeneic CAR T/CAR NK within 6 months of Day 1, or ongoing requirement for systemic graft-versus-host therapy
- Plasma cell leukemia defined as a plasma cell count >2000/mm^3
- Washout periods from prior therapies:
- For all subjects (Regimens A, A1, B and B1), receipt of the following: Chemotherapy, or radiation therapy, except for palliative purposes, within 14 days prior to Day 1 or five half-lives, whichever is shorter; Investigational therapy within 30 days prior to the first dose of study treatment or five half-lives, whichever is shorter; Biologic therapy (except for anti-CD38 mAbs), including antibody-drug conjugates or bi-specific immune-cell engaging antibody within 30 days prior to Day 1
- For subjects in Regimens B and B1 only, receipt of the following: Anti-CD38 therapy alone or in combination within 3 months prior to the start of daratumumab