title: Phase I study of cord blood-derived natural killer cells combined with autologous stem cell transplantation in multiple myeloma.
abstract: Multiple myeloma (MM) is a disease with known immune dysregulation. Natural killer (NK) cells have shown preclinical activity in MM. We conducted a first-in-human study of umbilical cord blood-derived (CB) NK cells for MM patients undergoing high dose chemotherapy and autologous haematopoietic stem cell transplantation (auto-HCT). Patients received lenalidomide (10 mg) on days -8 to -2, melphalan 200 mg/m2on day -7, CB-NK cells on day -5 and auto-HCT on day 0. Twelve patients were enrolled, three on each of four CB-NK cell dose levels: 5 × 106, 1 × 107, 5 × 107and 1 × 108CB-NK cells/kg. Ten patients had either high-risk chromosomal changes or a history of relapsed/progressed disease. There were no infusional toxicities and no graft-versus-host disease. One patient failed to engraft due to poor autologous graft quality and was rescued with a back-up autologous graft. Overall, 10 patients achieved at least a very good partial response as their best response, including eight with near complete response or better. With a median follow-up of 21 months, four patients have progressed or relapsed, two of whom have died. CB-NK cells were detected in vivo in six patients, with an activated phenotype (NKG2D+/NKp30+). These data warrant further development of this novel cellular therapy.
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Shah
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: McCarty
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Indreshpal
authors.initials: I
authors.lastname: Kaur
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Yvon
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Hila
authors.initials: H
authors.lastname: Shaim
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Muharrem
authors.initials: M
authors.lastname: Muftuoglu
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Enli
authors.initials: E
authors.lastname: Liu
authors.affiliation: Department of Lymphoma/Myeloma, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.affiliation: Department of Pediatrics, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Cooper
authors.affiliation: Department of Hematology & Oncology, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Dean
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Simrit
authors.initials: S
authors.lastname: Parmar
authors.affiliation: Department of Laboratory Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Cao
authors.affiliation: Institute of Human Nutrition, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Sobieiski
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Rima
authors.initials: R
authors.lastname: Saliba
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Chitra
authors.identifier: 0000-0003-0409-5556
authors.initials: C
authors.lastname: Hosing
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sairah
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yago
authors.initials: Y
authors.lastname: Nieto
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Qaiser
authors.initials: Q
authors.lastname: Bashir
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Krina
authors.initials: K
authors.lastname: Patel
authors.affiliation: Departments of Allergy and Immunology and Blood and Marrow Transplantation, Children's National Health System and George Washington University, Washington, DC, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Bollard
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Muzaffar
authors.initials: M
authors.lastname: Qazilbash
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Katy
authors.initials: K
authors.lastname: Rezvani
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002469:Cell Separation / Q000379:methods; D003131:Combined Modality Therapy; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D005434:Flow Cytometry / Q000379:methods; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007694:Killer Cells, Natural / Q000637:transplantation*; D000077269:Lenalidomide; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D000077269:Lenalidomide; D008558:Melphalan
keywords: autologous transplant; cord blood; ex vivo expansion; myeloma; natural killer