Journal of clinical oncology, 2013-11-20, Vol.31 (33), p.4199-4206
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.
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.
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.
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.
Hematologic and hematopoietic diseases ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Biological and medical sciences ; Medical sciences ; Tumors ; United States ; Humans ; Middle Aged ; Antibodies, Monoclonal - adverse effects ; Fatigue - etiology ; Antibodies, Monoclonal - therapeutic use ; Male ; Programmed Cell Death 1 Receptor - antagonists & inhibitors ; Transplantation, Autologous ; Neutropenia - etiology ; Young Adult ; Lymphoma, Large B-Cell, Diffuse - therapy ; Aged, 80 and over ; Lymphoma, Large B-Cell, Diffuse - immunology ; Adult ; Female ; Chile ; Antibodies, Monoclonal - immunology ; Immune Tolerance - drug effects ; Drug Administration Schedule ; Treatment Outcome ; Combined Modality Therapy ; India ; Disease-Free Survival ; Lymphoma, Large B-Cell, Diffuse - blood ; Lymphocyte Count ; Aged ; Hematopoietic Stem Cell Transplantation - methods ; Israel ; Programmed Cell Death 1 Receptor - immunology ; Hema13 ; Hema16 ; ORIGINAL REPORTS
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