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: Reid W Merryman, Haesook T Kim, Pier Luigi Zinzani, Carmelo Carlo-Stella, Stephen M Ansell, Miguel-Angel Perales, Abraham Avigdor, Ahmad S Halwani, Roch Houot, Tony Marchand, Nathalie Dhedin, Willy Lescaut, Anne Thiebaut-Bertrand, Sylvie François, Aspasia Stamatoullas-Bastard, Pierre-Simon Rohrlich, Hélène Labussière Wallet, Luca Castagna, Armando Santoro, Veronika Bachanova, Scott C Bresler, Amitabh Srivastava, Harim Kim, Emily Pesek, Marie Chammas, Carol Reynolds, Vincent T Ho, Joseph H Antin, Jerome Ritz, Robert J Soiffer, Philippe Armand
• Journal: Blood (Blood) Vol. 129 Issue 10 Pg. 1380-1388 (03 09 2017) ISSN: 1528-0020 [Electronic] United States
• PMID: 28073785 (Publication Type: Journal Article)
• Copyright: © 2017 by The American Society of Hematology.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor
• Nivolumab
• pembrolizumab

Topics

• Adult
• Aged
• Allografts
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Combined Modality Therapy
• Disease-Free Survival
• Female
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Kaplan-Meier Estimate
• Lymphoma (mortality, therapy)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (mortality, therapy)
• Nivolumab
• Programmed Cell Death 1 Receptor (antagonists & inhibitors)
• Retrospective Studies
• Statistics, Nonparametric
• Young Adult