TY - JOUR
T1 - Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplantation
AU - Ciurea, Stefan O.
AU - Schafer, Jolie R.
AU - Bassett, Roland
AU - Denman, Cecele J.
AU - Cao, Kai
AU - Willis, Dana
AU - Rondon, Gabriela
AU - Chen, Julianne
AU - Soebbing, Doris
AU - Kaur, Indreshpal
AU - Gulbis, Alison
AU - Ahmed, Sairah
AU - Rezvani, Katayoun
AU - Shpall, Elizabeth J.
AU - Lee, Dean A.
AU - Champlin, Richard E.
N1 - Funding Information:
This work was supported in part by MD Anderson Cancer Center support grants from the National Institutes of Health, National Cancer Institute (P30 CA016672 and P01 CA49639), Leukemia & Lymphoma Society Translational Research Program Award 6149-14, the Cancer Prevention Research Institute of Texas (RP110553), The University of Texas MD Anderson Cancer Center AML Moonshot Program and High Impact Clinical Research Support Program, the McKee Family Foundation, and the Taylor Trudeau Cycle for Life Charitable Foundation.
Publisher Copyright:
© 2017 by The American Society of Hematology.
PY - 2017/10/19
Y1 - 2017/10/19
N2 - Relapse has emerged as the most important cause of treatment failure after allogeneic hematopoietic stem cell transplantation (HSCT). To test the hypothesis that natural killer (NK) cells can decrease the risk of leukemia relapse, we initiated a phase 1 doseescalation study of membrane-bound interleukin 21 (mbIL21) expanded donor NK cells infused before and after haploidentical HSCT for high-risk myeloid malignancies. The goals were to determine the safety, feasibility, and maximum tolerated dose. Patients received a melphalan-based reduced-intensity conditioning regimen and posttransplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis. NK cells were infusedon days22,17, and128 posttransplant. AllNKexpansions achieved the required cell number,and 11 of 13 patients enrolled received all 3 planned NK-cell doses (1×105/kg to 1 × 108/kg per dose). No infusional reactions or dose-limiting toxicities occurred. All patients engrafted with donor cells. Seven patients (54%) developed grade 1-2 acute GVHD (aGVHD), none developed grade 3-4 aGVHD or chronic GVHD, and a low incidence of viral complications was observed. One patient died of nonrelapse mortality; 1 patient relapsed. All others were alive and in remission at last follow-up (median, 14.7 months). NK-cell reconstitutionwasquantitatively, phenotypically, and functionally superior compared with a similar group of patients not receiving NK cells. In conclusion, this trial demonstrated production feasibility and safety of infusing high doses of ex vivo-expanded NK cells after haploidentical HSCT without adverse effects, increased GVHD, or higher mortality, and was associated with significantly improved NK-cell number and function, lower viral infections, and low relapse rate posttransplant.
AB - Relapse has emerged as the most important cause of treatment failure after allogeneic hematopoietic stem cell transplantation (HSCT). To test the hypothesis that natural killer (NK) cells can decrease the risk of leukemia relapse, we initiated a phase 1 doseescalation study of membrane-bound interleukin 21 (mbIL21) expanded donor NK cells infused before and after haploidentical HSCT for high-risk myeloid malignancies. The goals were to determine the safety, feasibility, and maximum tolerated dose. Patients received a melphalan-based reduced-intensity conditioning regimen and posttransplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis. NK cells were infusedon days22,17, and128 posttransplant. AllNKexpansions achieved the required cell number,and 11 of 13 patients enrolled received all 3 planned NK-cell doses (1×105/kg to 1 × 108/kg per dose). No infusional reactions or dose-limiting toxicities occurred. All patients engrafted with donor cells. Seven patients (54%) developed grade 1-2 acute GVHD (aGVHD), none developed grade 3-4 aGVHD or chronic GVHD, and a low incidence of viral complications was observed. One patient died of nonrelapse mortality; 1 patient relapsed. All others were alive and in remission at last follow-up (median, 14.7 months). NK-cell reconstitutionwasquantitatively, phenotypically, and functionally superior compared with a similar group of patients not receiving NK cells. In conclusion, this trial demonstrated production feasibility and safety of infusing high doses of ex vivo-expanded NK cells after haploidentical HSCT without adverse effects, increased GVHD, or higher mortality, and was associated with significantly improved NK-cell number and function, lower viral infections, and low relapse rate posttransplant.
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U2 - 10.1182/blood-2017-05-785659
DO - 10.1182/blood-2017-05-785659
M3 - Article
C2 - 28835441
AN - SCOPUS:85032226079
SN - 0006-4971
VL - 130
SP - 1857
EP - 1868
JO - Blood
JF - Blood
IS - 16
ER -