title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Philippe 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.
authors.forename: Philippe
authors.initials: P
authors.lastname: Armand
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Edie A
authors.initials: EA
authors.lastname: Weller
authors.forename: Steven M
authors.initials: SM
authors.lastname: Devine
authors.forename: David E
authors.initials: DE
authors.lastname: Avigan
authors.forename: Yi-Bin
authors.initials: YB
authors.lastname: Chen
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kaminski
authors.forename: H Kent
authors.initials: HK
authors.lastname: Holland
authors.forename: Jane N
authors.initials: JN
authors.lastname: Winter
authors.forename: James R
authors.initials: JR
authors.lastname: Mason
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Fay
authors.forename: David A
authors.initials: DA
authors.lastname: Rizzieri
authors.forename: Chitra M
authors.initials: CM
authors.lastname: Hosing
authors.forename: Edward D
authors.initials: ED
authors.lastname: Ball
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Uberti
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.forename: Markus Y
authors.initials: MY
authors.lastname: Mapara
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Gregory
authors.forename: John M
authors.initials: JM
authors.lastname: Timmerman
authors.forename: David
authors.initials: D
authors.lastname: Andorsky
authors.forename: Reuven
authors.initials: R
authors.lastname: Or
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
authors.forename: Rinat
authors.initials: R
authors.lastname: Rotem-Yehudar
authors.forename: Leo I
authors.initials: LI
authors.lastname: Gordon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002677:Chile; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005221:Fatigue / Q000209:etiology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007194:India; D007557:Israel; D018655:Lymphocyte Count; D016403:Lymphoma, Large B-Cell, Diffuse / Q000097:blood / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C585832:pidilizumab