Phase I study of cord blood-derived natural killer cells combined with autologous stem cell transplantation in multiple myeloma

Br J Haematol. 2017 May;177(3):457-466. doi: 10.1111/bjh.14570. Epub 2017 Mar 14.

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/m2 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: 5 × 106 , 1 × 107 , 5 × 107 and 1 × 108 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 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.

Keywords: autologous transplant; cord blood; ex vivo expansion; myeloma; natural killer.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adoptive Transfer / methods
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cell Separation / methods
  • Combined Modality Therapy
  • Female
  • Fetal Blood / immunology*
  • Flow Cytometry / methods
  • Graft Survival
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Killer Cells, Natural / transplantation*
  • Lenalidomide
  • Male
  • Melphalan / administration & dosage
  • Middle Aged
  • Multiple Myeloma / therapy*
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives
  • Treatment Outcome

Substances

  • Thalidomide
  • Lenalidomide
  • Melphalan