A CME-certified Oncology Exchange Program Jointly provided by Potomac Center for Medical Education and Rockpointe Supported by an educational grant from Seattle Genetics, Inc.
Re-treatment with BV Bartlett et al., J of Hematolgoy Oncology 2014
Pet-adapted Sequential Salvage Therapy With BV Followed By Augmented ICE For Patients With Relapsed And Refractory HL A Non-Randomized, Open-label, Single-centre, Phase 2 Study Moskowitz A et al., 2015, The Lancet Oncology, 16(3), 284 292.
Pet-adapted Sequential Salvage Therapy With BV Followed By Augmented ICE For Patients With Relapsed And Refractory HL A Non-Randomized, Open-label, Single-centre, Phase 2 Study Tumour reduction after BV. Data shows PET status according to the Deauville scores of 1 5. Overall Survival (A), Event-free Survival (B), And Event-free Survival For Patients Who Received Transplantation, According To Their PET Status And Treatment Group (C) Moskowitz A et al., 2015, The Lancet Oncology, 16(3), 284 292.
Overall Survival (A), Event-free Survival (B), And EFS For Patients Who Received Transplantation, According To Their PET Status And Treatment Group (C) Moskowitz A et al., 2015, The Lancet Oncology, 16(3), 284 292.
Summary 76 % PET-negative (CR) achieved with PET adapted sequential therapy with BV and augmented ICE 27% patients avoided ICE salvage therapy HDT/ASCT outcomes were identical for patients who achieved PET-negative status after one or two sequential salvage regimens. The findings from this trial imply the goal of salvage therapy should be attainment of PET-negative status before HDT/ASCT for patients with relapsed or refractory Hodgkin's lymphoma. Moskowitz A et al., 2015, The Lancet Oncology, 16(3), 284 292.
BV as Consolidation post-asct In Patients With HL At Risk Of Relapse Or Progression (AETHERA) A Randomized, Double-blind, Placebo-controlled, Phase 3 Trial *Two patients allocated to the placebo group received a dose of brentuximab vedotin. Moskowitz C, et al. The Lancet, 2015.
PFS and OS Independent Review Investigator Assessment Interim Analysis of Overall Survival Moskowitz C, et al. The Lancet, 2015.
Subgroup Analysis of PFS by Independent Review Moskowitz C, et al. The Lancet, 2015.
Immunomodulation in HL: A novel approach PD-1 Pathway and immune surveillance PD-1 is expressed on the surface of activated T cells 1 Its ligands, PD-L1 and PD-L2, are overexpressed in certain tumor cells 1 Binding of PD-1 to its ligands inhibits T-cell activation, allowing tumors to evade the immune response 2 Pardoll et al Nat Rev Cancer. 2012; 2. Keir et al. Annu Rev Immunol. 2008
PD-L1 Almost Universally Expressed on RS Cells Through 9p24.1 Amplification or EBV > 80% expression in HL Green, et al. Blood 2010, Green, et al. CCR 2012.
PD-1/PD-L1 Inhibitors in Development For Lymphoma PD-1 inhibitors Nivolumab Fully human IgG4 anti-pd-1 antibody Pembrolizumab Humanized IgG4 anti-pd-1 antibody FDA approved for advanced or unresectable melanoma (September 2014) Pidilizumab Humanized anti-pd-1 IgG1 antibody Evaluated as maintenance following ASCT in high risk relapsed/refractory DLBCL (Armand, et al. JCO 2013) PD-L1 inhibitors MED14736 (MedImmune) MPDL3280A (Genentech/Roche)
Comparison of Agents Nivolumab (n=23) Abstract 289 Pembrolizumab (n=31) Abstract 290 Dose 1mg/kg 3mg/kg 10 mg/kg IV q 2 wk Week 1,4 and then q 2 % Prior ASCT 78 69 % Prior Brentuximab 78 100 % Grade 3 Toxicity 22 10 Lymphopenia, elevated lipase, colitis, pneumonitis Hypoxia, pneumonitis, joint swelling, axillary pain Grade 4 Toxicity 0 0 PD-L1 expression in samples tested 100% 100%
ASH 2014: Anti PD-1 Antibody Relapsed/Refractory HL, Brentuximab Failures Nivolumab: BMS-936558 Pembrolizumab:MK-3475 ORR 87%, CR 17% 6 m PFS 86%, med DOR NR Armand et al abstract 289 ORR 66% CR 21% med DOR NR (1-185+ d) Moskowitz et al abstract 290
Anti-PD-1 Take Home Points Significant activity seen with anti-pd-1 therapy in Hodgkin lymphoma Nivolumab: 87% ORR, 17% CR, 13% SD Pembrolizumab: 66% OR, 21% CR, 45% SD Both drugs with acceptable toxicity profile Breakthrough designation granted for nivolumab in HL International phase II study of nivolumab in HL is ongoing