Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma
Roch Houot
(1, 2)
,
Tony Marchand
(2, 1)
,
Nathalie Dhédin
(3)
,
Willy Lescaut
(4)
,
Anne Thiebaut-Bertrand
(5)
,
Sylvie Francois
(6)
,
Aspasia Stamatoullas-Bastard
(7)
,
Pierre-Simon Rohrlich
(8)
,
Hélène Labussière Wallet
(9)
,
Luca Castagna
(10, 11)
,
Armando Santoro
(12)
,
Veronika Bachanova
(13)
,
Scott C. Bresler
(14)
,
Amitabh Srivastava
(14)
,
Harim Kim
(15)
,
Emily Pesek
(14)
,
Marie Chammas
(14)
,
Carol Reynolds
(14)
,
Vincent T. Ho
(14)
,
Joseph H. Antin
(14)
,
Jerome Ritz
(14)
,
Robert J. Soiffer
(14)
,
Philippe Armand
(14)
,
Reid W. Merryman
(16)
,
Haesook T. Kim
(16)
,
Pier Luigi Zinzani
(17)
,
Carmelo Carlo-Stella
(18)
,
Stephen M. Ansell
(19)
,
Miguel-Angel Perales
(20)
,
Abraham Avigdor
(21)
,
Ahmad S. Halwani
(22)
1
Service d'hématologie clinique
2 MICMAC - Microenvironment, Cell Differentiation, Immunology and Cancer
3 Hôpital Saint-Louis
4 Centre Hospitalier Princesse Grace
5 Clinique Universitaire d'Hématologie [La Tronche, Grenoble]
6 Service des maladies du sang [Angers]
7 CLCC Henri Becquerel - Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen
8 Hôpital l'Archet
9 HCL - Hospices Civils de Lyon
10 IPC - Institut Paoli-Calmettes
11 IRCCS Milan - Istituto Clinico Humanitas [Milan]
12 Department of Oncology and Hematology
13 UMN - University of Minnesota [Twin Cities]
14 HMS - Harvard Medical School [Boston]
15 Seoul National University College of Medicine
16 Dana-Farber Cancer Institute [Boston]
17 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
18 UNIMI - Università degli Studi di Milano = University of Milan
19 Mayo Clinic [Rochester]
20 Memorial Sloane Kettering Cancer Center [New York]
21 Chaim Sheba Medical Center
22 Huntsman Cancer Institute [Salt Lake City]
2 MICMAC - Microenvironment, Cell Differentiation, Immunology and Cancer
3 Hôpital Saint-Louis
4 Centre Hospitalier Princesse Grace
5 Clinique Universitaire d'Hématologie [La Tronche, Grenoble]
6 Service des maladies du sang [Angers]
7 CLCC Henri Becquerel - Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen
8 Hôpital l'Archet
9 HCL - Hospices Civils de Lyon
10 IPC - Institut Paoli-Calmettes
11 IRCCS Milan - Istituto Clinico Humanitas [Milan]
12 Department of Oncology and Hematology
13 UMN - University of Minnesota [Twin Cities]
14 HMS - Harvard Medical School [Boston]
15 Seoul National University College of Medicine
16 Dana-Farber Cancer Institute [Boston]
17 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
18 UNIMI - Università degli Studi di Milano = University of Milan
19 Mayo Clinic [Rochester]
20 Memorial Sloane Kettering Cancer Center [New York]
21 Chaim Sheba Medical Center
22 Huntsman Cancer Institute [Salt Lake City]
Roch Houot
- Fonction : Auteur
- PersonId : 767105
- ORCID : 0000-0003-1729-8213
Philippe Armand
- Fonction : Auteur correspondant
- PersonId : 769020
- ORCID : 0000-0001-6098-1603
Pier Luigi Zinzani
- Fonction : Auteur
- PersonId : 782100
- ORCID : 0000-0002-2112-2651
Carmelo Carlo-Stella
- Fonction : Auteur
- PersonId : 782101
- ORCID : 0000-0003-3144-0124
Miguel-Angel Perales
- Fonction : Auteur
- PersonId : 782102
- ORCID : 0000-0002-5910-4571
Résumé
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.