Adult Bone Marrow Transplantation Service, Memorial Sloan ...€¦ · – Board Member: ASTCT, Be...
Transcript of Adult Bone Marrow Transplantation Service, Memorial Sloan ...€¦ · – Board Member: ASTCT, Be...
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Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center
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Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center
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Miguel Perales MD Disclosures
• Member, Scientific Advisory Board: – MolMed, NexImmune
• Ad hoc Advisory Board: – Abbvie, Bellicum, Incyte, Nektar Therapeutics, Novartis, Takeda
• Member, DSMB: – Medigene, Servier
• Consulting: – Merck
• Research Funding: – Incyte (clinical trial), Miltenyi (clinical trial), Kite/Gilead (clinical trial)
• Academic/Not-for-Profit: – Board Member: ASTCT, Be The Match (NMDP) – CIBMTR CIDR Executive Committee– Tufts Cancer Center DSMB, University of Barcelona CAR T trial DSMB
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Miguel Perales MD Disclosures
• Member, Scientific Advisory Board: – MolMed, NexImmune
• Ad hoc Advisory Board: – Abbvie, Bellicum, Incyte, Nektar Therapeutics, Novartis, Takeda
• Member, DSMB: – Medigene, Servier
• Consulting: – Merck
• Research Funding: – Incyte (clinical trial), Miltenyi (clinical trial), Kite/Gilead (clinical trial)
• Academic/Not-for-Profit: – Board Member: ASTCT, Be The Match (NMDP) – CIBMTR CIDR Executive Committee– Tufts Cancer Center DSMB, University of Barcelona CAR T trial DSMB
• I perform alloHCT for Hodgkin Lymphoma
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A Debate with Craig “I don’t believe in allo” Moskowitz?....
Moskowitz et al, Blood. 2001; 97:616-623
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Use of Allo-HCT in Relapsed / Refractory Hodgkin Lymphoma is declining.
Courtesy of A Sureda - EBMT Lymphoma Database, with permission
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HLA-Id Sib WMUD 10/10 CB Haplo
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BMT
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New drugs for Hodgkin LymphomaSo many choices …
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Brentuximab Vedotin is effective in relapsed/ refractory Hodgkin Lymphoma
Younes et al, J Clin Oncol. 2012 Jun 20;30(18):2183-9
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Post ASCT Brentuximab Vedotin increases PFS in patients with high risk HL
Moskowitz et al, Lancet 2015
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The programmed cell death protein 1 (PD-1) immunologic checkpoint.
Michael A. Postow et al. JCO 2014
©2015 by American Society of Clinical Oncology
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Single-agent activity of PD-1/PD-L1 axis blockade in different tumor types
Matsuki & Younes, Curr. Treat. Options in Oncol. 2016
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HODGKIN LYMPHOMA
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HRS Cells Express High Levels of PDL-1
9p24.1 Gene amplification
EBV Infection
JAK2
PDL1
Hodgkin and Reed Sternberg (HRS) Cells
CD30
HRS
PD1
PD-L1
PD-L2 MHC I/II
TCR
T cell
Adapted from Stathis & Younes: Ann Oncology 2015And Younes A & Ansell S : Seminars in Hematology, 2016, 186–18
T-Cells T-Cells
PD1
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Anti-PD1 Ab are effective in HL patients post ASCT who relapse after or fail Brentuximab Vedotin
A. Younes, Lancet Hem 2016 P. Armand, JCO 2016
Nivolumab Pembrolizumab
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Keynote 087 – PembrolizumabBest ORR by Blinded Central Review
Chen, Moskowitz, JCO 2017
CR 21.7% 24.7% 20.0% 22.4%
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Checkmate 205 – NivolumabBest ORR by Blinded Central Review
Armand et al, JCO 2018
CR 29% 13% 12% 16%
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Chemo-Free Approaches to Treat RR HL
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Chemo-Free Approaches to Treat RR HL
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Long Term Outcome after Relapse post-Auto-SCT is Poor in Patients with high risk RR Hodgkin Lymphoma
Martínez C et al, Ann Oncol 2013
Early relapse after auto-HSCT (< 6 mo)/ Stage IV disease at auto-HSCT/ Bulky disease
Age > 45 yrs/ Poor performance status
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Patients who do not achieve CR with salvage BV had much lower OS and PFS
Chen et al, Blood. 2016;128(12):1562-1566)
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Extended Follow-up of the Phase 2 Single-Arm CheckMate 205 Study
Armand et al, ASH 2018
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Impact of Brentuximab on Allo-HCT
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Brentuximab Vedotin Is Associated with Improved PFS after AlloHCT for Hodgkin Lymphoma
R. Chen et al. / Biol Blood Marrow Transplant 20 (2014) 1841e1868
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Improving the Results of Allo-HCT in the Brentuximab Vedotin Era
Hegerova et al, BMT 2017
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Prior BV does not affect post Allo-HCT PFS or OS
PFS OS
Bazarbachi A et al, Br J Haematol 2018
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Impact of Checkpoint Inhibitors on Allo-HCT
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Is AlloHCT stuck on the wrong side of Checkpoint Charlie?
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Allo-HCT can be safely performed in patients after checkpoint inhibitors
RW Merryman et al, Blood 2017
Relapse NRM
N = 39, anti-PD1 @ median 57 days (7-260) prior to HCT
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Allo-HCT can be safely performed in patients after checkpoint inhibitors
OS PFS
N = 39, anti-PD1 @ median 57 days (7-260) prior to HCT
RW Merryman et al, Blood 2017
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A febrile syndrome is observed in a number of patients after prior anti-PD1
aGVHD: 1-yr CI of gr 2-4 44%, & gr 3-4 23% cGVHD: 1yr 41%.
RW Merryman et al, Blood 2017
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CRS after Haplo-PBSCT post anti-PD1 responded to Tocilizumab
Cho & Perales, BMT 2016
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OS and PFS in HL after AlloHCT in Patients treated with Nivolumab
Armand et al, JCO 2018
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OS and PFS are encouraging in patients with HL treated with Nivolumab after Allo-HCT
Charles Herbaux et al. Blood 2017;129:2471-2478
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Early nivolumab initiation is associated with development of nivolumab-induced GVHD
Charles Herbaux et al. Blood 2017;129:2471-2478
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Response characteristics in patients with HL receiving nivolumab for a relapse after allo-HCT.
Charles Herbaux et al. Blood 2017;129:2471-2478
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Frequency of treatment-emergent aGVHD and cGVHD and responses to treatment of GVHD.
Bradley M. Haverkos et al. Blood 2017;130:221-228
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Cumulative incidence of clinically significant events after anti–PD-1 administration.
Bradley M. Haverkos et al. Blood 2017;130:221-228
ORR = 77% (95% CI 58% to 90%) in 30 response assessable patients (15 CRs, 8 PRs, 3 SD, 4 POD)
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Outcomes after allo-HCT in Hodgkin Lymphoma are similar in different graft sources
Martínez C et al, J Clin Oncol 2017
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Results of AlloHCT in HL have improved over time
Sureda A et al, EHA 2018
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ASBMT Recommendations for Allogeneic HCT in Hodgkin Lymphoma
Perales et al, Biol Blood Marrow Transplant 21 (2015) 971-983
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ASBMT Recommendations for Allogeneic HCT in Hodgkin Lymphoma
Perales et al, Biol Blood Marrow Transplant 21 (2015) 971-983
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Allo-HCT should still be considered curative option for Hodgkin Lymphoma
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Improved AlloHCT OS
Decreased AlloHCTUsage
Excellent results of AlloHCT post CPI
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Perform Allogeneic HCT for Hodgkin’PD1-Inh