Ph I/II Trial of Cord Blood-derived NK Cells With NY-ESO-1 TCR/IL-15 for R/R Myeloma

Inclusion criteria

• . \> or = 2 prior lines of therapy (including exposure to at least one proteasome inhibitor, immunomodulatory imide drug \[ImiD\], and anti-cd38 antibody and refractory to the last line of therapy)
• . Have measurable disease (serum monoclonal \[M\] protein level ≥ 0.5 g/dL, and/or urine M protein level ≥ 200 mg/24hrs, and/or involved serum free light chain \[FLC\] level ≥10 mg/dL provided the serum-free light-chain ratio is abnormal) \*\* Refractory is defined as a documented progressive disease during or within 60 days (measured from the last dose of any drug within the regimen) of completing treatment with the last anti-myeloma regimen before study entry 4. No anti-myeloma therapy within 7 days of lymphodepleting therapy. Note: Steroids are allowed at any time up until lymphodepletion. Localized radiation for palliation is allowed at any time up until NK cell infusion 5. Prior autologous/allogeneic transplants are allowed. 6. Prior cell therapy is allowed against targets other than NY-ESO-1. 7. Patients must have recovered from systemic toxicity of prior anti-myeloma therapy at the start of lymphodepletion 8. Eastern Cooperative Oncology Group (ECOG) performance status \<= 2 9. Estimated glomerular filtration rate (eGFR using the Chronic Kidney Disease Epidemiology Collaboration \[CKI-EPI\] equation) \>= 30 ml/min/1.73 m\^2 10. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =\< 2.5 x upper limit of normal (ULN) or =\< 5 x ULN if documented liver metastases 11. Total bilirubin =\< 1.5 mg/dL, except in subjects with Gilbert's syndrome in whom total bilirubin must be =\< 3.0 mg/dL 12. No history of liver cirrhosis 13. No ascites 14. Cardiac ejection fraction \>= 50% 15. No clinically significant pericardial effusion as determined by an ECHO or MUGA 16. No uncontrolled arrhythmias or symptomatic cardiac disease 17. No clinically significant pleural effusion (per principal investigator \[PI\] discretion) 18. Baseline oxygen saturation \> 92% on room air 19. Able to provide written informed consent 20. 18-80 years of age 21. Weight ≥ 40 kg 22. Absolute neutrophil count (ANC) ≥ 1000 /
• . Cardiac arrhythmias not controlled with medical management