WS-CART-CS1 for the Treatment of Patients with Recurrent or Refractory Multiple Myeloma

Inclusion Criteria

• Relapsed or refractory multiple myeloma after 3 or more prior lines of therapy, including proteasome inhibitor (e.g. bortezomib or carfilzomib), anti-CD38 therapy (e.g. daratumumab), and anti-BCMA therapies (e.g. BCMA bispecific antibodies or BCMA CAR-T)
• Measurable disease, defined as meeting at least one of the following criteria: * Serum monoclonal (M)-protein ≥ 0.5 g/dL * Urine M-protein ≥ 200 mg/24 hour (h) * Serum free light chain (FLC) assay: involved FLC level ≥ 10 mg/dL (100 mg/L) with abnormal serum FLC ratio * A biopsy-proven plasmacytoma * Bone marrow plasma cells > 30% of total bone marrow cells
• At least 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Calculated creatinine clearance ≥ 50 mL/min/1.73 m^2 OR
• Radioisotope glomerular filtration rate ≥ 50 mL/min/1.73 m^2 OR
• Normal serum creatinine based on age/gender per institutional normal range
• Alanine transaminase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) ≤ 5 x upper limit of normal (ULN) for age
• Total bilirubin ≤ 2.0 x institutional (I)ULN (unless the patient has grade 1 bilirubin elevation due to Gilbert's disease or a similar syndrome involving slow conjugation of bilirubin)
• Minimum level of pulmonary reserve defined as oxygen saturation > 91% measured by pulse oximetry on room air
• Left ventricular ejection fraction (LVEF) ≥ 45% confirmed by echocardiogram or multigated acquisition (MUGA) within 28 days of screening
• The effects of CS1 CAR-T on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (at least 2 forms of contraception, including one barrier method) prior to study entry and for 12 months after CS1 CAR-T infusion. If a female subject or female partner of a male subject becomes pregnant during therapy or within 12 months following WS-CART-CS1 infusion, the investigator must be notified in order to facilitate outcome follow-up
• Ability to understand and willingness to sign an Institutional Review Board (IRB)-approved written informed consent document (or that of legally authorized representative, if applicable)

Exclusion Criteria

• Any prior systemic therapy for multiple myeloma within 14 days before planned day of leukapheresis
• A history of other malignancy with the exception of treated non-melanomatous skin cancers and malignancies for which all treatment was completed at least 2 years before registration and the subject has no evidence of disease
• Currently receiving any other investigational agents
• Receipt of any cellular therapy within 8 weeks prior to the planned start of conditioning
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to CS1 CAR-T or other agents used in the study
• History of grade 3 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) with other CAR-Ts (including BCMA CAR)
• Active hepatitis B, active hepatitis C, any uncontrolled infection, or HIV infection
• Ongoing or active infection or other serious underlying medical condition that would impair the ability to receive protocol treatment
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry