Decrease post-transplant relapse using donor-derived expanded NK-cells

• Published in: Leukemia Vol. 36; no. 1; pp. 155 - 164
• Main Authors: Ciurea, Stefan O, Kongtim, Piyanuch, Soebbing, Doris, Trikha, Prashant, Behbehani, Gregory, Rondon, Gabriela, Olson, Amanda, Bashir, Qaiser, Gulbis, Alison M, Indreshpal, Kaur, Rezvani, Katayoun, Shpall, Elizabeth J, Bassett, Roland, Cao, Kai, Martin, Andrew St, Devine, Steven, Horowitz, Mary, Pasquini, Marcelo, Lee, Dean A, Champlin, Richard E
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.01.2022; Nature Publishing Group UK
• Subjects: Adolescent; Adult; Aged; Antibodies; Case-Control Studies; Cytotoxicity; Female; Follow-Up Studies; Hematologic Neoplasms - immunology; Hematologic Neoplasms - pathology; Hematologic Neoplasms - therapy; Hematopoietic Stem Cell Transplantation - mortality; Histocompatibility antigen HLA; Humans; Immune reconstitution; Interleukin 21; Killer cell immunoglobulin-like receptors; Killer Cells, Natural - immunology; Killer Cells, Natural - transplantation; Lymphocytes T; Male; Middle Aged; Natural killer cells; Neoplasm Recurrence, Local - immunology; Neoplasm Recurrence, Local - pathology; Neoplasm Recurrence, Local - therapy; NKG2 antigen; Patients; Phenotypes; Prognosis; Stem cell transplantation; Stem cells; Survival Rate; Transplantation; Transplantation Conditioning; Transplantation, Haploidentical; Transplants & implants; Unrelated Donors - statistics & numerical data; Young Adult
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/s41375-021-01349-4

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 × 10 -1 × 10 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://clinicaltrials.gov/ct2/show/NCT01904136 ).