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

> 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 m² 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 /

Note: Growth factor support is allowed prior to lymphodepletion chemotherapy (LD chemo). Transfusion support is allowed at any time. If cytopenias are related to multiple myeloma, the patient may proceed without meeting above hematologic parameters only if bone marrow plasma cells are >= 50% 19. Hemoglobin ≥ 8 g/dL

Note: Growth factor support is allowed prior to LD chemo. Transfusion support is allowed at any time. If cytopenias are related to multiple myeloma, the patient may proceed without meeting above hematologic parameters only if bone marrow plasma cells are >= 50% 20. Platelet count >= 25,000 /uL