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www.chicagolymphoma.com
Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center
Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center
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
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
A Debate with Craig “I don’t believe in allo” Moskowitz?....
Moskowitz et al, Blood. 2001; 97:616-623
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
BMT
New drugs for Hodgkin LymphomaSo many choices …
Brentuximab Vedotin is effective in relapsed/ refractory Hodgkin Lymphoma
Younes et al, J Clin Oncol. 2012 Jun 20;30(18):2183-9
Post ASCT Brentuximab Vedotin increases PFS in patients with high risk HL
Moskowitz et al, Lancet 2015
The programmed cell death protein 1 (PD-1) immunologic checkpoint.
Michael A. Postow et al. JCO 2014
©2015 by American Society of Clinical Oncology
Single-agent activity of PD-1/PD-L1 axis blockade in different tumor types
Matsuki & Younes, Curr. Treat. Options in Oncol. 2016
HODGKIN LYMPHOMA
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
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
Keynote 087 – PembrolizumabBest ORR by Blinded Central Review
Chen, Moskowitz, JCO 2017
CR 21.7% 24.7% 20.0% 22.4%
Checkmate 205 – NivolumabBest ORR by Blinded Central Review
Armand et al, JCO 2018
CR 29% 13% 12% 16%
Chemo-Free Approaches to Treat RR HL
Chemo-Free Approaches to Treat RR HL
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
Patients who do not achieve CR with salvage BV had much lower OS and PFS
Chen et al, Blood. 2016;128(12):1562-1566)
Extended Follow-up of the Phase 2 Single-Arm CheckMate 205 Study
Armand et al, ASH 2018
Impact of Brentuximab on Allo-HCT
Brentuximab Vedotin Is Associated with Improved PFS after AlloHCT for Hodgkin Lymphoma
R. Chen et al. / Biol Blood Marrow Transplant 20 (2014) 1841e1868
Improving the Results of Allo-HCT in the Brentuximab Vedotin Era
Hegerova et al, BMT 2017
Prior BV does not affect post Allo-HCT PFS or OS
PFS OS
Bazarbachi A et al, Br J Haematol 2018
Impact of Checkpoint Inhibitors on Allo-HCT
Is AlloHCT stuck on the wrong side of Checkpoint Charlie?
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
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
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
CRS after Haplo-PBSCT post anti-PD1 responded to Tocilizumab
Cho & Perales, BMT 2016
OS and PFS in HL after AlloHCT in Patients treated with Nivolumab
Armand et al, JCO 2018
OS and PFS are encouraging in patients with HL treated with Nivolumab after Allo-HCT
Charles Herbaux et al. Blood 2017;129:2471-2478
Early nivolumab initiation is associated with development of nivolumab-induced GVHD
Charles Herbaux et al. Blood 2017;129:2471-2478
Response characteristics in patients with HL receiving nivolumab for a relapse after allo-HCT.
Charles Herbaux et al. Blood 2017;129:2471-2478
Frequency of treatment-emergent aGVHD and cGVHD and responses to treatment of GVHD.
Bradley M. Haverkos et al. Blood 2017;130:221-228
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)
Outcomes after allo-HCT in Hodgkin Lymphoma are similar in different graft sources
Martínez C et al, J Clin Oncol 2017
Results of AlloHCT in HL have improved over time
Sureda A et al, EHA 2018
ASBMT Recommendations for Allogeneic HCT in Hodgkin Lymphoma
Perales et al, Biol Blood Marrow Transplant 21 (2015) 971-983
ASBMT Recommendations for Allogeneic HCT in Hodgkin Lymphoma
Perales et al, Biol Blood Marrow Transplant 21 (2015) 971-983
Allo-HCT should still be considered curative option for Hodgkin Lymphoma
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HLA-Id Sib WMUD 10/10 CB Haplo
Improved AlloHCT OS
Decreased AlloHCTUsage
Excellent results of AlloHCT post CPI
Perform Allogeneic HCT for Hodgkin’PD1-Inh
