General AML

ASCO 2018 | Early results from parallel phase I studies of haploidentical expanded NK cells after fludarabine/cytarabine in R/R AML

At the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, Stefan O. Ciurea from The University Texas MD Anderson Cancer Center presented early data from two parallel phase I studies (NCT01787474), investigating the safety and efficacy of mbIL21-expanded haploidentical natural killer (NK) cells after induction chemotherapy with fludarabine, cytarabine, and G-CSF (FLAG).

In total, 13 relapsed/refractory (R/R) acute myeloid leukemia (AML) patients (median age = 52 years, range: 12–70) were enrolled in these parallel phase I studies at the MDACC (n = 8) and a center in Brazil (n = 5). Haploidentical NK cell donors were selected by KIR ligand and/or KIR gene content. Patients received three NK cell infusions per week for two weeks, beginning 3–10 days after chemotherapy at a dose of 1 x 106 NK cells/kg/infusion (n = 8), 5 x 106 (n = 3) and 1x 107 NK/cells/kg/infusion (n = 2). Response was assessed at Day 30 after treatment.

Key findings:
  • Day 30 Complete remission (CR)/CR with incomplete blood count recovery (CRi) rate: 69% (9/13)
  • Persistent Minimal Residual Disease (by flow cytometry/PCR) at Day 30 in patients in CR/CRi: 89% (8/9)
  • Median time to best response: 26.5 days (range: 19–62)
  • Treatment-related mortality (TRM): 0% (0/13)
  • Relapse rate: 54% (7/13)
    • Median time to relapse: 55 days (18–211)
  • Allogeneic stem cell transplantation was performed in 38% (5/13) of patients
    • TRM: 40% (5/13)
    • Relapse rate: 20% (1/5)
  • At the time of last follow-up (median follow-up = 202 days, range: 39–590), 38% of patients were alive and in CR

The speaker, Stefan Ciurea, concluded by stating that “infusions of ex vivo NK cells appear safe” with high response rates observed in patients with refractory AML at lower NK cell dose levels.

Both parallel studies continue to accrue patients at higher NK cell dose levels which the speaker hopes would aid in clearing persistent MRD in patients.

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