Inclusion Criteria:
Subjects must meet ALL of the following criteria to be eligible for study enrollment:
1. Age: ≥18 years at time of signing informed consent
2. Diagnosis: Documented multiple myeloma meeting one of the following:
* Relapsed disease: Progression after achieving at least minimal response (MR) to prior therapy
* Refractory disease: Non-responsive or progressive disease while on therapy or within 60 days of last treatment (in subjects who achieved ≥MR on prior therapy)
3. Prior Therapy:
* Received ≥3 prior lines of anti-myeloma therapy
* Prior therapy must include:
At least one proteasome inhibitor At least one immunomodulatory drug (e.g., lenalidomide, pomalidomide, thalidomide) At least one anti-CD38 monoclonal antibody (e.g., daratumumab, isatuximab) o Prior anti-BCMA CAR-T therapy is permitted if subject achieved PFS ≥6 months post-infusion
4. Measurable Disease: At least one of the following at screening (for response assessment eligibility):
* Serum M-protein ≥0.5 g/dL by protein electrophoresis (SPEP)
* Urine M-protein ≥200 mg/24 hours by protein electrophoresis (UPEP)
* Serum free light chain (FLC) difference ≥10 mg/dL with abnormal FLC ratio Note: Subjects with non-measurable disease may enroll for safety assessment
5. Performance Status: ECOG Performance Status 0-2 (see Appendix A)
6. Organ Function: Adequate organ function as defined by:
Hepatic:
o Total bilirubin ≤2× institutional upper limit of normal (ULN), except subjects with Gilbert's syndrome
* AST and ALT ≤2.5× institutional ULN
Renal:
o Calculated creatinine clearance ≥30 mL/min (Cockcroft-Gault formula)
Cardiac:
o Left ventricular ejection fraction (LVEF) ≥45% by echocardiogram or MUGA
Pulmonary:
o ≤Grade 1 dyspnea
o Oxygen saturation ≥92% on room air
o If PFTs performed: FEV₁ ≥50% predicted and DLCO ≥40% predicted (corrected for hemoglobin)
7. Prior Therapy Washout:
o ≥2 weeks since last radiation or systemic anti-myeloma therapy (standard agents)
o ≥4 weeks since last investigational therapy
o ≥6 weeks since autologous stem cell transplant
8. Informed Consent: Ability to understand and willingness to provide written informed consent
9. Contraception Requirements (for subjects of reproductive potential):
Female subjects:
o Women of childbearing potential must: Have negative serum pregnancy test at screening Agree to use highly effective contraception (failure rate \<1% per year) from enrollment through 6 months post-CAR-T infusion
* Acceptable methods: bilateral tubal ligation, male partner sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing IUD, copper IUD
* Sexual abstinence is acceptable if consistent with subject's preferred lifestyle
Male subjects:
* Must agree to use condom plus effective contraception if partner is of childbearing potential
* Must refrain from sperm donation from enrollment through 6 months post-CAR-T infusion
Exclusion Criteria:
Subjects meeting ANY of the following criteria will be excluded:
1. Disease-Specific Exclusions:
* Active CNS involvement by multiple myeloma
* Plasma cell leukemia
* History of allogeneic hematopoietic stem cell transplantation
2. Malignancy Exclusions:
o Second active malignancy, except: Non-melanoma skin cancer Carcinoma in situ (cervix, bladder, breast) Stage 1 uterine cancer Localized prostate cancer
3. Cardiovascular Exclusions:
* New York Heart Association (NYHA) Class IV congestive heart failure
* Unstable angina pectoris
* Clinically significant cardiac arrhythmias
* Myocardial infarction, stroke, or TIA within 6 months of enrollment
4. Infectious Disease Exclusions:
* Known HIV infection or AIDS-related illness
* Active hepatitis B or C infection:
Positive HBsAg, or Positive anti-HBc or anti-HCV with detectable viral nucleic acid by PCR
* Active infection requiring systemic therapy 5. Neurological Exclusions:
* History of clinically relevant CNS pathology including:
Epilepsy or seizure disorders Paresis, aphasia Uncontrolled cerebrovascular disease Severe brain injury Dementia Parkinson's disease 6. Autoimmune Disease:
* Active autoimmune disease requiring systemic immunosuppression \>15 mg/day prednisone equivalent within past 6 months
* Examples: rheumatoid arthritis, lupus
