title: Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma.
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.
authors.affiliation: Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Reid W
authors.initials: RW
authors.lastname: Merryman
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Haesook T
authors.initials: HT
authors.lastname: Kim
authors.affiliation: Institute of Hematology "L. e A. Seràgnoli," University of Bologna, Bologna, Italy.
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Zinzani
authors.affiliation: Humanitas Clinical & Research Center, Milan, Italy.|Department of Oncology and Hematology, University of Milan, Milan, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Carlo-Stella
authors.affiliation: Mayo Clinic, Rochester, MN.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
authors.affiliation: Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Miguel-Angel
authors.initials: MA
authors.lastname: Perales
authors.affiliation: Division of Hematology and Bone-Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Avigdor
authors.affiliation: Huntsman Cancer Institute, Salt Lake City, UT.
authors.forename: Ahmad S
authors.initials: AS
authors.lastname: Halwani
authors.affiliation: Centre Hospitalier Universitaire (CHU) Rennes, Service Hématologie Clinique, Rennes, France.|INSERM, Rennes, France.
authors.forename: Roch
authors.initials: R
authors.lastname: Houot
authors.affiliation: Centre Hospitalier Universitaire (CHU) Rennes, Service Hématologie Clinique, Rennes, France.
authors.forename: Tony
authors.initials: T
authors.lastname: Marchand
authors.affiliation: Hôpital Saint Louis, Service Hématologie Adolescents et Jeunes Adultes, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dhedin
authors.affiliation: Centre Hospitalier Princesse Grace, Service Médecine Interne et Onco-Hématologie, Monaco, France.
authors.forename: Willy
authors.initials: W
authors.lastname: Lescaut
authors.affiliation: CHU Grenoble, Clinique Universitaire d'Hématologie, Grenoble, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Thiebaut-Bertrand
authors.affiliation: CHU Angers, Service Maladies du Sang, Angers, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: François
authors.affiliation: Centre Henri Becquerel, Service Hématologie Clinique, Rouen, France.
authors.forename: Aspasia
authors.initials: A
authors.lastname: Stamatoullas-Bastard
authors.affiliation: CHU Nice, Service Hématologie et Onco-Hématologie Pédiatrique, Nice, France.
authors.forename: Pierre-Simon
authors.initials: PS
authors.lastname: Rohrlich
authors.affiliation: Hospices Civils de Lyon, Service d'Hématologie Clinique, Lyon, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Labussière Wallet
authors.affiliation: Humanitas Clinical & Research Center, Milan, Italy.|Department of Oncology and Hematology, University of Milan, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Castagna
authors.affiliation: Humanitas Clinical & Research Center, Milan, Italy.|Department of Oncology and Hematology, University of Milan, Milan, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
authors.affiliation: Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN.
authors.forename: Veronika
authors.initials: V
authors.lastname: Bachanova
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Bresler
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and.
authors.forename: Amitabh
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: University College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Harim
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Emily
authors.initials: E
authors.lastname: Pesek
authors.affiliation: Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Marie
authors.initials: M
authors.lastname: Chammas
authors.affiliation: Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Carol
authors.initials: C
authors.lastname: Reynolds
authors.affiliation: Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
authors.affiliation: Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.affiliation: Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
authors.affiliation: Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.affiliation: Division of Hematologic Malignancies and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Philippe
authors.initials: P
authors.lastname: Armand
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008223:Lymphoma / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000628:therapy; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; C582435:pembrolizumab