In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 8_suppl ( 2019-03-10), p. 74-74
Abstract:
74 Background: NK cells have potent antitumor and antiviral effects. We hypothesized that multiple infusions of high doses of mb-IL21 ex vivo expanded NK cells administered peri-transplant will enhance graft-versus-leukemia effect and decrease viral reactivation. Methods: In the phase 1 dose escalation study patients received NK cells starting at 1x10 5 to 1x10 8 /Kg/dose (N = 13). No dose limiting toxicities were observed. In the phase 2 study, 12 patients with myeloid malignancies received mbIL-21 ex vivo expanded NK cells at dose 1x10 8 NK cells/kg with a K562 feeder cell system and with 41BB. NK cells were generated from peripheral blood mononuclear cells of the same donor and infused fresh on day -2, and cryopreserved on day +7 and +28. Conditioning regimen consisted of melphalan, fludarabine and TBI. All patients had bone marrow graft. Here we report updated results of all patients treated to date on this study. Results: Twenty-five patients (18 AML/MDS and 7 CML) were treated to date. The median age was 45 years, the median follow-up of survivors was 28 months. 16/18 AML/MDS patients had high-risk disease. No adverse effects occurred. Engraftment was achieved in all 24 evaluable patients after a median of 19 days. The cumulative incidence (CI) of grade 2 aGVHD was 38% at day 100. No chronic GVHD was observed. The CI of TRM was 21% at 2 years. The CI of relapse at 1 year was 8%. The 2-years PFS was 66%. Ten patients reactivated CMV. Immunologic reconstitution of T cell subsets showed a 5.7 fold higher number of NK cells on day 28 in patients who received highest NK cell doses vs. others. A matched-pair analysis done with an independent CIBMTR cohort of patients who received either MAC (N = 61) or RIC (N = 57), showed a significantly improvement in relapse rate and PFS in favor of patients treated on trial. Conclusions: Administration of higher doses of NK cells was associated with higher NK cell numbers early post-transplant, suggesting that a dose-dependent effect could be achieved. A low relapse rate and lower viral reactivation post-transplant continues to be seen, suggesting that NK cells exert both anti-tumor and antiviral effects in this setting. Clinical trial information: NCT01904136.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2019.37.8_suppl.74
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2019
detail.hit.zdb_id:
2005181-5
