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Blood ; 130(2): 221-228, 2017 07 13.
Article in English | MEDLINE | ID: mdl-28468799

ABSTRACT

Given the limited treatment options for relapsed lymphoma post-allogeneic hematopoietic cell transplantation (post-allo-HCT) and the success of programmed death 1 (PD-1) blockade in classical Hodgkin lymphoma (cHL) patients, anti-PD-1 monoclonal antibodies (mAbs) are increasingly being used off-label after allo-HCT. To characterize the safety and efficacy of PD-1 blockade in this setting, we conducted a multicenter retrospective analysis of 31 lymphoma patients receiving anti-PD-1 mAbs for relapse post-allo-HCT. Twenty-nine (94%) patients had cHL and 27 had ≥1 salvage therapy post-allo-HCT and prior to anti-PD-1 treatment. Median follow-up was 428 days (range, 133-833) after the first dose of anti-PD-1. Overall response rate was 77% (15 complete responses and 8 partial responses) in 30 evaluable patients. At last follow-up, 11 of 31 patients progressed and 21 of 31 (68%) remain alive, with 8 (26%) deaths related to new-onset graft-versus-host disease (GVHD) after anti-PD-1. Seventeen (55%) patients developed treatment-emergent GVHD after initiation of anti-PD-1 (6 acute, 4 overlap, and 7 chronic), with onset after a median of 1, 2, and 2 doses, respectively. GVHD severity was grade III-IV acute or severe chronic in 9 patients. Only 2 of these 17 patients achieved complete response to GVHD treatment, and 14 of 17 required ≥2 systemic therapies. In conclusion, PD-1 blockade in relapsed cHL allo-HCT patients appears to be highly efficacious but frequently complicated by rapid onset of severe and treatment-refractory GVHD. PD-1 blockade post-allo-HCT should be studied further but cannot be recommended for routine use outside of a clinical trial.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal/administration & dosage , Graft vs Host Disease/chemically induced , Hematopoietic Stem Cell Transplantation , Hodgkin Disease/therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Adult , Aged , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents/therapeutic use , Female , Gene Expression , Graft vs Host Disease/immunology , Graft vs Host Disease/mortality , Graft vs Host Disease/pathology , Hodgkin Disease/immunology , Hodgkin Disease/mortality , Hodgkin Disease/pathology , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Nivolumab , Programmed Cell Death 1 Receptor/genetics , Programmed Cell Death 1 Receptor/immunology , Remission Induction , Retrospective Studies , Salvage Therapy/methods , Survival Analysis , Transplantation Conditioning , Transplantation, Homologous , Treatment Outcome
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