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Anas Younes, M.D. Memorial Sloan Kettering Cancer Center

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1 Anas Younes, M.D. Memorial Sloan Kettering Cancer Center
Recurrent HL after Auto Transplant in CR on Brentuximab Vedotin: Allo Transplant or Maintenance Therapy? Anas Younes, M.D. Memorial Sloan Kettering Cancer Center

2 Relapse After ASCT: OS by Era of Transplant
Overall Survival <1990 median 1.9 yrs median 2.6 yrs >2000* median 1.9 yrs >2000 vs : P (Gehan) = .02, P (logrank) = .03 Arai S et al, Leukemia and Lymphoma 2013

3 or GVD after failing a prior transplant (dashed line).
Gemcitabine, Vinorelbine, and Pegylated Liposomal Doxorubicin (GVD) Followed by Autologous Stem-Cell Transplant (solid line) or GVD after failing a prior transplant (dashed line). Bartlett N et al. Ann Oncol 2007;18:

4 94% (96 of 102) of patients achieved tumour reduction
Brentuximab Vedotin: Pivotal Phase II Trial Maximum Tumour Reduction per IRF 94% (96 of 102) of patients achieved tumour reduction Individual patients (n=98*) Tumour size (% change from baseline) 100 50 –50 –100 Complete remission by PET Younes et al. JCO 2012

5 Brentuximab Vedotin: Pivotal Phase II Trial PFS Results by Best Response
Phase II pivotal study of brentuximab vedotin in 102 patients with relapsed/refractory HL post ASCT: PFS by best response

6 Summary Results of Phase I/II Single Agents in Patients with Relapsed HL
Response rate (%) Younes a, Hematology/Oncology Clinics of North America 2013

7 Single Agent Activity of New Agents in Post SCT Relapsed cHL Comparison to multiagent chemotherapy GVD % Response rate Younes a et al. ASCO 2012

8 Brentuximab Vedotin Initial treatment vs. Retreatment
HL sALCL N= N=15 N= N=8 Bartlet et al. ASCO 2012

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12 Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin’s lymphoma. Results of the HDR-ALLO study – a prospective clinical trial by the Grupo Español de Linfomas/Trasplante de Médula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation Sureda A, et al: Haematologica February; 97(2): 310–317.

13 RIC and Allo SCT for Relapsed/Refractory HL
Non Relapse Mortality Relapse Incidence Impact of disease chemosensitivity on relapse incidence. Sureda A, et al: Haematologica February; 97(2): 310–317.

14 RIC and Allo SCT for Relapsed/Refractory HL
PFS

15 70% of HRS cells have B2MG mutations
Integrated Genomic Analysis of Flow Sorted Hodgkin and Reed-Sternberg Cell in Primary Classical Hodgkin Lymphoma Jonathan Reichel (New York, USA) 70% of HRS cells have B2MG mutations

16 Allo Transplant for Relapsed cHL?
ABVD N=100 Relapse/Refractory (n=30) Respond to salvage therapy and offered ASCT (n=24) Cured with ASCT (n=12) R/R to ASCT Respond to salvage therapy and have a suitable donor (n=6) 20% TRM + 40% relapse (n=4) Cured with allo SCT (N=2) with GVHD Refratory or no suitable donor ASCT ineligible Cure (n=70)

17 Proposed Algorithm for Treating Patients Post ASCT
<CR/Relapse Brentuximab Vedotin CR Observe <CR Consider allo SCT Consider evaluation for B2MG mutations Observe (Role of adjuvant BV?)


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