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

• Type of Material: Article
• Authors: Edmund Waller, Emory University
• Language: English
• Date: 2013-11-20
• Publisher: American Society of Clinical Oncology
• Publication Version: Final Published Version
• Copyright Statement: © 2013 by American Society of Clinical Oncology
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.2012.48.3685
• Title of Journal or Parent Work: Journal of Clinical Oncology
• ISSN: 0732-183X
• Volume: 31
• Issue: 33
• Start Page: 4199
• End Page: 4206
• Grant/Funding Information: P.A. was supported by an American Society of Hematology (ASH) Scholar Award and by an American Society of Clinical Oncology/Conquer Cancer Foundation Career Development Award.; D.A.R. was supported by an ASH Scholar Award.
• Keywords: SAFETY; SALVAGE CHEMOTHERAPY; PD-1; MARROW TRANSPLANTATION; Oncology; MONOCLONAL-ANTIBODY; HEMATOLOGIC MALIGNANCIES; Life Sciences & Biomedicine; POSITRON-EMISSION-TOMOGRAPHY; RECONSTITUTION; Science & Technology; NON-HODGKINS-LYMPHOMA; IMMUNOTHERAPY
• Research Categories: Health Sciences, Immunology; Health Sciences, Oncology

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.