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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Improved AlloHCT OS

Decreased AlloHCTUsage

Excellent results of AlloHCT post CPI

Perform Allogeneic HCT for Hodgkin’PD1-Inh