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

Philippe Armand, Arnon Nagler, Edie A. Weller, Steven M. Devine, David E. Avigan, Yi Bin Chen, Mark S. Kaminski, H. Kent Holland, Jane N. Winter, James R. Mason, Joseph W. Fay, David A. Rizzieri, Chitra M. Hosing, Edward D. Ball, Joseph P. Uberti, Hillard M. Lazarus, Markus Y. Mapara, Stephanie A. Gregory, John M. Timmerman, David AndorskyReuven Or, Edmund K. Waller, Rinat Rotem-Yehudar, Leo I. Gordon*

*Corresponding author for this work

Research output: Contribution to journalArticle

328 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4199-4206
Number of pages8
JournalJournal of Clinical Oncology
Volume31
Issue number33
DOIs
StatePublished - Nov 20 2013

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Armand, P., Nagler, A., Weller, E. A., Devine, S. M., Avigan, D. E., Chen, Y. B., Kaminski, M. S., Holland, H. K., Winter, J. N., Mason, J. R., Fay, J. W., Rizzieri, D. A., Hosing, C. M., Ball, E. D., Uberti, J. P., Lazarus, H. M., Mapara, M. Y., Gregory, S. A., Timmerman, J. M., ... Gordon, L. I. (2013). 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. Journal of Clinical Oncology, 31(33), 4199-4206. https://doi.org/10.1200/JCO.2012.48.3685