Off the Shelf NK Cell Therapy Feasible in R/R Acute Myeloid Leukemia, Myelodysplastic Syndrome

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.

REFERENCE

Vasu S, Sharma. N, Wall SA, et al. A Phase I Clinical Trial Testing the Safety of IL-21-Expanded, Third-Party Donor-Derived Natural Killer Cells for Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome. Presented at: Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; April 23-26, 2022; Salt Lake City, UT. Abstract 276.