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.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Armand, P; Nagler, A; Weller, EA; Devine, SM; Avigan, DE; Chen, Y-B; Kaminski, MS; Holland, HK; Winter, JN; Mason, JR; Fay, JW; Rizzieri, DA; Hosing, CM; Ball, ED; Uberti, JP; Lazarus, HM; Mapara, MY; Gregory, SA; Timmerman, JM; Andorsky, D; Or, R; Waller, EK; Rotem-Yehudar, R; Gordon, LI

Published Date

  • November 20, 2013

Published In

Volume / Issue

  • 31 / 33

Start / End Page

  • 4199 - 4206

PubMed ID

  • 24127452

Pubmed Central ID

  • 24127452

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

Digital Object Identifier (DOI)

  • 10.1200/JCO.2012.48.3685

Language

  • eng

Conference Location

  • United States