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

Reid W. Merryman, Haesook T. Kim, Pier Luigi Zinzani, Carmelo Carlo-Stella, Stephen Maxted 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 BachanovaScott 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

Research output: Contribution to journalArticle

79 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1380-1388
Number of pages9
JournalBlood
Volume129
Issue number10
DOIs
StatePublished - Mar 9 2017

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Transplants
Hematopoietic Stem Cells
Stem cells
Refractory materials
Lymphoma
Safety
Grafts
Graft vs Host Disease
T-cells
Confidence Intervals
Programmed Cell Death 1 Receptor
Incidence
Hepatic Veno-Occlusive Disease
Lymphocytes
T-Lymphocytes
Recurrence
Lymphocyte Subsets
Regulatory T-Lymphocytes
Toxicity
Disease-Free Survival

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Merryman, R. W., Kim, H. T., Zinzani, P. L., Carlo-Stella, C., Ansell, S. M., Perales, M. A., ... Armand, P. (2017). Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma. Blood, 129(10), 1380-1388. https://doi.org/10.1182/blood-2016-09-738385

Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma. / Merryman, Reid W.; Kim, Haesook T.; Zinzani, Pier Luigi; Carlo-Stella, Carmelo; Ansell, Stephen Maxted; Perales, Miguel Angel; Avigdor, Abraham; Halwani, Ahmad S.; Houot, Roch; Marchand, Tony; Dhedin, Nathalie; Lescaut, Willy; Thiebaut-Bertrand, Anne; François, Sylvie; Stamatoullas-Bastard, Aspasia; Rohrlich, Pierre Simon; Wallet, Hélène Labussière; Castagna, Luca; Santoro, Armando; Bachanova, Veronika; Bresler, Scott C.; Srivastava, Amitabh; Kim, Harim; Pesek, Emily; Chammas, Marie; Reynolds, Carol; Ho, Vincent T.; Antin, Joseph H.; Ritz, Jerome; Soiffer, Robert J.; Armand, Philippe.

In: Blood, Vol. 129, No. 10, 09.03.2017, p. 1380-1388.

Research output: Contribution to journalArticle

Merryman, RW, Kim, HT, Zinzani, PL, Carlo-Stella, C, Ansell, SM, Perales, MA, Avigdor, A, Halwani, AS, Houot, R, Marchand, T, Dhedin, N, Lescaut, W, Thiebaut-Bertrand, A, François, S, Stamatoullas-Bastard, A, Rohrlich, PS, Wallet, HL, Castagna, L, Santoro, A, Bachanova, V, Bresler, SC, Srivastava, A, Kim, H, Pesek, E, Chammas, M, Reynolds, C, Ho, VT, Antin, JH, Ritz, J, Soiffer, RJ & Armand, P 2017, 'Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma', Blood, vol. 129, no. 10, pp. 1380-1388. https://doi.org/10.1182/blood-2016-09-738385
Merryman, Reid W. ; Kim, Haesook T. ; Zinzani, Pier Luigi ; Carlo-Stella, Carmelo ; Ansell, Stephen Maxted ; Perales, Miguel Angel ; Avigdor, Abraham ; Halwani, Ahmad S. ; Houot, Roch ; Marchand, Tony ; Dhedin, Nathalie ; Lescaut, Willy ; Thiebaut-Bertrand, Anne ; François, Sylvie ; Stamatoullas-Bastard, Aspasia ; Rohrlich, Pierre Simon ; Wallet, Hélène Labussière ; Castagna, Luca ; Santoro, Armando ; Bachanova, Veronika ; Bresler, Scott C. ; Srivastava, Amitabh ; Kim, Harim ; Pesek, Emily ; Chammas, Marie ; Reynolds, Carol ; Ho, Vincent T. ; Antin, Joseph H. ; Ritz, Jerome ; Soiffer, Robert J. ; Armand, Philippe. / Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma. In: Blood. 2017 ; Vol. 129, No. 10. pp. 1380-1388.
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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.",
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AU - Houot, Roch

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AU - Dhedin, Nathalie

AU - Lescaut, Willy

AU - Thiebaut-Bertrand, Anne

AU - François, Sylvie

AU - Stamatoullas-Bastard, Aspasia

AU - Rohrlich, Pierre Simon

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AU - Bachanova, Veronika

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