Decrease post-transplant relapse using donor-derived expanded NK-cells
Stefan O Ciurea, Piyanuch Kongtim, Doris Soebbing, Prashant Trikha, Gregory Behbehani, Gabriela Rondon, Amanda Olson, Qaiser Bashir, Alison M Gulbis, Kaur Indreshpal, Katayoun Rezvani, Elizabeth J Shpall, Roland Bassett, Kai Cao, Andrew St Martin, Steven Devine, Mary Horowitz, Marcelo Pasquini, Dean A Lee, Richard E Champlin, Stefan O Ciurea, Piyanuch Kongtim, Doris Soebbing, Prashant Trikha, Gregory Behbehani, Gabriela Rondon, Amanda Olson, Qaiser Bashir, Alison M Gulbis, Kaur Indreshpal, Katayoun Rezvani, Elizabeth J Shpall, Roland Bassett, Kai Cao, Andrew St Martin, Steven Devine, Mary Horowitz, Marcelo Pasquini, Dean A Lee, Richard E Champlin
Abstract
In this phase I/II clinical trial, we investigated the safety and efficacy of high doses of mb-IL21 ex vivo expanded donor-derived NK cells to decrease relapse in 25 patients with myeloid malignancies receiving haploidentical stem-cell transplantation (HSCT). Three doses of donor NK cells (1 × 105-1 × 108 cells/kg/dose) were administered on days -2, +7, and +28. Results were compared with an independent contemporaneously treated case-matched cohort of 160 patients from the CIBMTR database.After a median follow-up of 24 months, the 2-year relapse rate was 4% vs. 38% (p = 0.014), and disease-free survival (DFS) was 66% vs. 44% (p = 0.1) in the cases and controls, respectively. Only one relapse occurred in the study group, in a patient with the high level of donor-specific anti-HLA antibodies (DSA) presented before transplantation. The 2-year relapse and DFS in patients without DSA was 0% vs. 40% and 72% vs. 44%, respectively with HR for DFS in controls of 2.64 (p = 0.029). NK cells in recipient blood were increased at day +30 in a dose-dependent manner compared with historical controls, and had a proliferating, mature, highly cytotoxic, NKG2C+/KIR+ phenotype.Administration of donor-derived expanded NK cells after haploidentical transplantation was safe, associated with NK cell-dominant immune reconstitution early post-transplant, preserved T-cell reconstitution, and improved relapse and DFS. TRIAL REGISTRATION: NCT01904136 ( https://ichgcp.net/clinical-trials-registry/NCT01904136 ).
Conflict of interest statement
SOC served as advisory board member for Cellularity, CareDx, Kiadis, Spectrum, CytoSen, MolMed, received research funds from Miltenyi Biotech and Kiadis, and has intellectual property and equity in Kiadis. PK served as advisory board member for CareDx. PT has intellectual property licensing to Kiadis Pharma. DAL received consulting fees, equity, and intellectual property in Kiadis Pharma. Consulting fees and equity in Courier Therapeutics, Consulting fees for Caribou Biosciences. All other authors had no potential conflict of interest to declare.
© 2021. The Author(s).
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Source: PubMed