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Blood. 2017 Mar 9;129(10):1380-1388. doi: 10.1182/blood-2016-09-738385. Epub 2017 Jan 10.

Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma.

Author information

1
Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
2
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.
3
Institute of Hematology "L. e A. Seràgnoli," University of Bologna, Bologna, Italy.
4
Humanitas Clinical & Research Center, Milan, Italy.
5
Department of Oncology and Hematology, University of Milan, Milan, Italy.
6
Mayo Clinic, Rochester, MN.
7
Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY.
8
Division of Hematology and Bone-Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel.
9
Huntsman Cancer Institute, Salt Lake City, UT.
10
Centre Hospitalier Universitaire (CHU) Rennes, Service Hématologie Clinique, Rennes, France.
11
INSERM, Rennes, France.
12
Hôpital Saint Louis, Service Hématologie Adolescents et Jeunes Adultes, Assistance Publique-Hôpitaux de Paris, Paris, France.
13
Centre Hospitalier Princesse Grace, Service Médecine Interne et Onco-Hématologie, Monaco, France.
14
CHU Grenoble, Clinique Universitaire d'Hématologie, Grenoble, France.
15
CHU Angers, Service Maladies du Sang, Angers, France.
16
Centre Henri Becquerel, Service Hématologie Clinique, Rouen, France.
17
CHU Nice, Service Hématologie et Onco-Hématologie Pédiatrique, Nice, France.
18
Hospices Civils de Lyon, Service d'Hématologie Clinique, Lyon, France.
19
Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN.
20
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and.
21
University College of Medicine, Seoul National University, Seoul, South Korea.

Abstract

Anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are being increasingly tested in patients with advanced lymphoma. Following treatment, many of those patients are likely to be candidates for allogeneic hematopoietic stem cell transplant (HSCT). However, the safety and efficacy of HSCT may be affected by prior PD-1 blockade. We conducted an international retrospective analysis of 39 patients with lymphoma who received prior treatment with a PD-1 inhibitor, at a median time of 62 days (7-260) before HSCT. After a median follow-up of 12 months, the 1-year cumulative incidences of grade 2-4 and grade 3-4 acute graft-versus-host disease (GVHD) were 44% and 23%, respectively, whereas the 1-year incidence of chronic GVHD was 41%. There were 4 treatment-related deaths (1 from hepatic sinusoidal obstruction syndrome, 3 from early acute GVHD). In addition, 7 patients developed a noninfectious febrile syndrome shortly after transplant requiring prolonged courses of steroids. One-year overall and progression-free survival rates were 89% (95% confidence interval [CI], 74-96) and 76% (95% CI, 56-87), respectively. One-year cumulative incidences of relapse and nonrelapse mortality were 14% (95% CI, 4-29) and 11% (95% CI, 3-23), respectively. Circulating lymphocyte subsets were analyzed in 17 patients. Compared with controls, patients previously treated with PD-1 blockade had significantly decreased PD-1+ T cells and decreased ratios of T-regulatory cells to conventional CD4 and CD8 T cells. In conclusion, HSCT after PD-1 blockade appears feasible with a low rate of relapse. However, there may be an increased risk of early immune toxicity, which could reflect long-lasting immune alterations triggered by prior PD-1 blockade.

PMID:
28073785
PMCID:
PMC5345733
DOI:
10.1182/blood-2016-09-738385
[Indexed for MEDLINE]
Free PMC Article

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