A phase I trial of NK-92 cells for refractory hematological malignancies relapsing after autologous hematopoietic cell transplantation shows safety and evidence of efficacy

Abstract

Background: Autologous NK cell therapy can treat a variety of malignancies, but is limited by patient-specific variations in potency and cell number expansion. In contrast, allogeneic NK cell lines can overcome many of these limitations. Cells from the permanent NK-92 line are constitutively activated, lack inhibitory receptors and appear to be safe based on two prior phase I trials.

Materials and methods: We conducted a single-center, non-randomized, non-blinded, open-label, Phase I dose-escalation trial of irradiated NK-92 cells in adults with refractory hematological malignancies who relapsed after autologous hematopoietic cell transplantation (AHCT). The objectives were to determine safety, feasibility and evidence of activity. Patients were treated at one of three dose levels (1 × 109 cells/m2, 3 × 109 cells/m2 and 5 × 109 cells/m2), given on day 1, 3 and 5 for a planned total of six monthly cycles.

Results: Twelve patients with lymphoma or multiple myeloma who relapsed after AHCT for relapsed/refractory disease were enrolled in this trial. The treatment was well tolerated, with minor toxicities restricted to acute infusional events, including fever, chills, nausea and fatigue. Two patients achieved a complete response (Hodgkin lymphoma and multiple myeloma), two patients had minor responses and one had clinical improvement on the trial.

Conclusions: Irradiated NK-92 cells can be administered at very high doses with minimal toxicity in patients with refractory blood cancers, who had relapsed after AHCT. We conclude that high dose NK-92 therapy is safe, shows some evidence of efficacy in patients with refractory blood cancers and warrants further clinical investigation.

Keywords: NK cell; NK-92; clinical trial; lymphoma; multiple myeloma.

Conflict of interest statement

CONFLICTS OF INTEREST AK received funding from Nantkwest unrelated to the clinical trial to conduct laboratory research with NK-92 and derivatives.

Figures

Figure 1

Cytokines were measured a various time points pre and post NK-92 infusions measuring: IL-2 (A) TNF-alpha (B) TNF-beta (C) INF-gamma (D) IL-6 (E) and IL-10 (F).

Figure 2

Patient 03 serial CT scans showing appearance of mesenteric lymph nodes prior to NK-92 administration (A) post 3- cycles of NK-92 (B) post 5-cycles of NK-92 therapy (C) and at long term follow-up 2 (D) and 5 (E) years after treatment.

Figure 3

Patient 03 serial CT scans showing appearance and progression of splenomegaly at baseline (A, 12.7 cm), post 5 cycles of NK-92 therapy (B, 15.3 cm) and long-term follow-up at two years post-treatment (C, 10.5 cm).