Off the Shelf NK Cell Therapy Feasible in R/R Acute Myeloid Leukemia, Myelodysplastic Syndrome
Preliminary findings from the phase 1 clinical trial demonstrate good cell persistence and expansion in vivo.
Initial data from a phase 1 trial examining the feasibility of third-party, donor-derived natural killer (NK) cells in patients with relapsed or refractory acute myeloid leukemia (R/R AMLY) or myelodysplastic syndrome demonstrated good safety and cell persistence, according to findings presented at the Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR (2022 Tandem Meetings), held in Salt Lake City, Utah, and virtually April 23-26, 2022.1
Recognizing the challenges associated with personalized donor-derived cell therapies, the investigator-initiated study, led by Sumithira Vasu, MD, of Ohio State University Comprehensive Cancer Center, worked to identify third-party NK cell donors in order to establish an off the shelf NK cell bank using membrane-bound interleukin-21 feeder cells and cryopreserved NK cells.
Goals of the open-label, dose-escalation study include determining the persistence of ex-vivo expanded, off the shelf, third-party donor cells; characterization of in vivo expansion of the cells and any differences based on conditioning regimen; and determination of immunophenotype and function of expanded cells. The study has a target enrollment of 30 participants that include adults with R/R AML who have received 1 to 3 prior lines of therapy.
Vasu and colleagues presented data on 6 treated patients, 3 of whom were in cohort 1 and were <60 years old and received fludarabine 30 mg/m2/day and cytarabine 2 g/m2/day on days -6 to –2; and 3 of whom were in cohort 2, were ≥60 years old and received fludarabine 30 mg/m2/day (days -5 to -2) and decitabine 20 mg/m2/day (days -6 to -2) followed by infusion of HLA-mismatched NK cells 3 times per week for 6 doses at the first dose level of 1x107 cells/kg/dose on days 0, 2, 4, 6, 8, and 10. Notably, 1 patient withdrew prior to NK cell infusion.
Overall, NK cell infusion was well-tolerated in the remaining 5 patients, all of whom received the total 6 doses over 2 weeks. One report of a cytokine release-type syndrome was reported in 1 patient, while 1 other proceeded to allogeneic hematopoietic stem cell transplant. Notably, no adverse events, including infusion-related reactions, neurotoxicity, or graft versus host disease were reported.
Following analysis with flow cytometry, the investigators concluded that NK cell persistence and expansion in vivo was superior in cohort 1 which underwent lymphodepletion with the fludarabine 30 mg/m2/day and cytarabine 2 g/m2/day regimen. Two of 3 patients in cohort 1 reached over 50% donor NK cells between day 0 and day 14 as a proportion of all mononuclear cells in peripheral blood.
“Cryopreserved, third-party donor-derived NK cells are safe and feasible in relapsed/refractory AML patients, and at this first dose level, completely HLA-mismatched NK cells can persist and expand to high levels in vivo,” concluded Vasu and colleagues.
For more coverage of the Tandem Meetings 2022, click here.
