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Clin Cancer Res. 2015 Sep 15;21(18):4055-61. doi: 10.1158/1078-0432.CCR-15-0304. Epub 2015 May 21.

A Phase I Trial of the Anti-KIR Antibody IPH2101 and Lenalidomide in Patients with Relapsed/Refractory Multiple Myeloma.

Author information

1
The Ohio State University Comprehensive Cancer Center, Columbus, Ohio. Don.benson@osumc.edu.
2
University of Pennsylvania Abramson Cancer Center, Philadelphia, Pennsylvania.
3
Mount Sinai School of Medicine, New York, New York.
4
Dana Farber Cancer Institute, Boston, Massachusetts. Boston VA Healthcare System, Harvard Medical School, Boston, Massachusetts.
5
St. Francis Hospital, Greenville, South Carolina.
6
The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
7
Innate Pharma, Marseille, France.

Abstract

PURPOSE:

Natural killer (NK) cells may play an important role in the immune response to multiple myeloma; however, multiple myeloma cells express killer immunoglobulin-like receptor (KIR) ligands to prevent NK cell cytotoxicity. Lenalidomide can expand and activate NK cells in parallel with its direct effects against multiple myeloma; however, dexamethasone may impair these favorable immunomodulatory properties. IPH2101, a first-in-class antiinhibitory KIR antibody, has acceptable safety and tolerability in multiple myeloma as a single agent. The present work sought to characterize lenalidomide and IPH2101 as a novel, steroid-sparing, dual immune therapy for multiple myeloma.

EXPERIMENTAL DESIGN:

A phase I trial enrolled 15 patients in three cohorts. Lenalidomide was administered per os at 10 mg on cohort 1 and 25 mg on cohorts 2 and 3 days 1 to 21 on a 28-day cycle with IPH2101 given intravenously on day 1 of each cycle at 0.2 mg/kg in cohort 1, 1 mg/kg in cohort 2, and 2 mg/kg in cohort 3. No corticosteroids were utilized. The primary endpoint was safety, and secondary endpoints included clinical activity, pharmacokinetics (PK), and pharmacodynamics (PD).

RESULTS:

The biologic endpoint of full KIR occupancy was achieved across the IPH2101 dosing interval. PD and PK of IPH2101 with lenalidomide were similar to data from a prior single-agent IPH2101 trial. Five serious adverse events (SAE) were reported. Five objective responses occurred. No autoimmunity was seen.

CONCLUSIONS:

These findings suggest that lenalidomide in combination with antiinhibitory KIR therapy warrants further investigation in multiple myeloma as a steroid-sparing, dual immune therapy. This trial was registered at www.clinicaltrials.gov (reference: NCT01217203).

PMID:
25999435
PMCID:
PMC4573800
DOI:
10.1158/1078-0432.CCR-15-0304
[Indexed for MEDLINE]
Free PMC Article

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