期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 177, 期 3, 页码 457-466出版社
WILEY
DOI: 10.1111/bjh.14570
关键词
myeloma; natural killer; cord blood; exvivo expansion; autologous transplant
类别
资金
- Celgene Corporation
- M.D. Anderson Cancer Center High Risk Multiple Myeloma Moon Shot
- Stading-Younger Cancer Research Foundation
- M.D. Anderson Molecular Evaluation and/or Biopsy Related Support Program (MEBRS)
- M.D. Anderson Cancer Center [P30 CA016672]
- Florence Maude Thomas Cancer
- National Cancer Institute [P50 CA142509, R01 CA184464, CA194264, U10 CA032102]
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 (10mg) on days -8 to -2, melphalan 200mg/m(2) on 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: 5x10(6), 1x10(7), 5x10(7) and 1x10(8) CB-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 21months, four patients have progressed or relapsed, two of whom have died. CB-NK cells were detected invivo in six patients, with an activated phenotype (NKG2D(+)/NKp30(+)). These data warrant further development of this novel cellular therapy.
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