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J Clin Oncol. 2013 Nov 20;31(33):4199-206. doi: 10.1200/JCO.2012.48.3685. Epub 2013 Oct 14.

Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase II trial.

Author information

  • 1Philippe Armand and Edie Weller, Dana-Farber Cancer Institute; David E. Avigan, Beth Israel Deaconess Medical Center; Yi-Bin Chen, Massachusetts General Hospital, Boston, MA; Arnon Nagler, Chaim Sheba Medical Center, Tel-Hashomer; Reuven Or, Hadassah Medical Center, Jerusalem; Rinat Rotem-Yehudar, CureTech, Yavne, Israel; Steven M. Devine, The Ohio State University Comprehensive Cancer Center, Ohio State University, Columbus; Hillard M. Lazarus, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH; Mark S. Kaminski, University of Michigan, Ann Arbor, MI; H. Kent Holland, Northside Hospital; Edmund K. Waller, Winship Cancer Institute, Emory University, Atlanta, GA; Jane N. Winter and Leo I. Gordon, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine; Stephanie A. Gregory, Rush Medical Center, Chicago, IL; James R. Mason, Scripps Clinic; Edward D. Ball, Moores University of California at San Diego Cancer Center, University of California, San Diego; John M. Timmerman and David Andorsky, University of California, Los Angeles, Los Angeles, CA; Joseph W. Fay, Baylor Research Institute, Baylor University Medical Center, Dallas; Chitra M. Hosing, The University of Texas MD Anderson Cancer Center, Houston, TX; David A. Rizzieri, Duke Cancer Center, Durham, NC; Joseph P. Uberti, Karmanos Cancer Institute, Detroit, MI; Markus Y. Mapara, University of Pittsburgh School of Medicine and Cancer Institute, Pittsburgh, PA.

Abstract

PURPOSE:

The Programmed Death-1 (PD-1) immune checkpoint pathway may be usurped by tumors, including diffuse large B-cell lymphoma (DLBCL), to evade immune surveillance. The reconstituting immune landscape after autologous hematopoietic stem-cell transplantation (AHSCT) may be particularly favorable for breaking immune tolerance through PD-1 blockade.

PATIENTS AND METHODS:

We conducted an international phase II study of pidilizumab, an anti-PD-1 monoclonal antibody, in patients with DLBCL undergoing AHSCT, with correlative studies of lymphocyte subsets. Patients received three doses of pidilizumab beginning 1 to 3 months after AHSCT.

RESULTS:

Sixty-six eligible patients were treated. Toxicity was mild. At 16 months after the first treatment, progression-free survival (PFS) was 0.72 (90% CI, 0.60 to 0.82), meeting the primary end point. Among the 24 high-risk patients who remained positive on positron emission tomography after salvage chemotherapy, the 16-month PFS was 0.70 (90% CI, 0.51 to 0.82). Among the 35 patients with measurable disease after AHSCT, the overall response rate after pidilizumab treatment was 51%. Treatment was associated with increases in circulating lymphocyte subsets including PD-L1E-bearing lymphocytes, suggesting an on-target in vivo effect of pidilizumab.

CONCLUSION:

This is the first demonstration of clinical activity of PD-1 blockade in DLBCL. Given these results, PD-1 blockade after AHSCT using pidilizumab may represent a promising therapeutic strategy in this disease.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00532259.

PMID:
24127452
[PubMed - indexed for MEDLINE]
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