Oncotarget

Clinical Research Papers:

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

Brent A. Williams, Arjun Datt Law, Bertrand Routy, Neal denHollander, Vikas Gupta, Xing-Hua Wang, Amélie Chaboureau, Sowmya Viswanathan and Armand Keating _

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Oncotarget. 2017; 8:89256-89268. https://doi.org/10.18632/oncotarget.19204

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Abstract

Brent A. Williams1, Arjun Datt Law1, Bertrand Routy1, Neal denHollander2, Vikas Gupta1, Xing-Hua Wang1, Amélie Chaboureau1, Sowmya Viswanathan1 and Armand Keating1

1Cell Therapy Program, Princess Margaret Cancer Centre, Toronto, ON, Canada

2Department of Laboratory Medicine, University Health Network, Toronto, ON, Canada

Correspondence to:

Armand Keating, email: armand.keating@uhn.ca

Keywords: NK cell, NK-92, clinical trial, lymphoma, multiple myeloma

Received: May 31, 2017     Accepted: June 28, 2017     Published: July 12, 2017

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.


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