Blood Journal
Leading the way in experimental and clinical research in hematology

A phase I trial of the anti-KIR antibody IPH2101 in patients with relapsed/refractory multiple myeloma

  1. Don M. Benson Jr.1,*,
  2. Craig C. Hofmeister2,
  3. Swaminathan Padmanabhan3,
  4. Attaya Suvannasankha4,
  5. Sundar Jagganath5,
  6. Rafat Abonour4,
  7. Courtney Bakan2,
  8. Pascale Andre6,
  9. Yvonne Efebera1,
  10. Jérôme Tiollier6,
  11. Michael A. Caligiuri1, and
  12. Sherif S. Farag3
  1. 1 Division of Hematology, The Ohio State University, Columbus, OH, United States;
  2. 2 The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States;
  3. 3 Cancer Treatment and Research Center, San Antonio, TX, United States;
  4. 4 Indiana University Cancer Center, Indianapolis, IN, United States;
  5. 5 Mount Sinai Medical Center, New York, NY, United States;
  6. 6 Innate Pharma, Marseille, France
  1. * Corresponding author; email: don.benson{at}osumc.edu

Abstract

Natural killer (NK) cells elicit cytotoxicity against multiple myeloma (MM); however, MM cells express HLA class I molecules as ligands to NK cell inhibitory killer immunoglobulin-like receptors (KIR) as a means of immunoevasion. KIR-ligand mismatch may improve outcomes in allogeneic transplantation for MM. Extrapolating on this concept, we conducted a phase I trial of IPH2101, an anti-KIR antibody, in patients with relapsed/refractory MM. IPH2101 was administered intravenously every 28 days in 7 dose-escalated cohorts (0.0003mg/kg - 3mg/kg) for up to 4 cycles. Pharmacokinetic, pharmacodynamic and correlative immunological studies were completed. 32 patients were enrolled. The biologic endpoint of full KIR2D occupancy across the dosing cycle was achieved without dose-limiting toxicity (DLT) or maximally tolerated dose (MTD). 1 severe adverse event (SAE) was noted. Pharmacokinetic and pharmacodynamic findings approximated preclinical predictions, and IPH2101 enhanced ex vivo pt-derived NK cell cytotoxicity against MM. No objective responses were seen. No evidence of autoimmunity was observed. These findings suggest IPH2101 is safe and tolerable at doses that achieve full inhibitory KIR saturation and this approach warrants further development in MM. This trial was registered at www.clinicaltrials.gov (reference: NCT00552396).

  • Submitted June 25, 2012.
  • Accepted September 21, 2012.