Alexander Fosså, M.D. PhD. Current position: Senior Consultant, Department of Medical Oncology Oslo University Hospital Focus of work: - Malignant lymphoma - Chemotherapy, immunotherapy, radiotherapy - Head of Nordic Lymphoma Working group for Hodgkin Lymphoma Specific expertise / current research interest: - Hodgkin Lymphoma - Castleman s disease - Cancer survivorship
PD-1 inhibition in Hodgkin lymphoma - case report Alexander Fosså MD PhD Department of Medical Oncology OUH Radium Hospital
Disclosures J&J : Roche: Honoraria Honoraria and research support
WHO for dummies Mantel cell lymphoma 6 % Hodgkin lymphoma 14 % Diffuse large B-cell lymphoma 31 % Burkitt lymphoma 2 % Follicular lymphoma 22 % Lymphocytic lymphoma 6 % WHO; World Health Organisation Lymphoplasmacytic lymphoma 1% Marginal zone lymphoma 5 % Lymphoblastic lymphoma 1 % Periperal T-cell lymphoma 6 % Anaplastic large cell lymphoma 2 % Courtesy of J. Delabie
Hodgkin lymphoma 120 patients in Norway per year 80 % cured in 1. line 10 % cured in 2. second line (mostly by ASCT) Patients with unmet medical need Relapse after ASCT and/or unable to undergo ASCT and failed brentuximab vedotin Elderly patients ASCT; autologous stem cell transplantation
Classical Hodgkin lymphoma - microenvironment CD30 CD3 Courtesy of S. Spetalen; Küppers et al., 2012
PD-L1 in Classical Hodgkin lymphoma Primary disease PD-L1 expression (IHC) 21 % (n=87) 1 87 % (n=38) 2 75 % (n=109) 6 Relapsed/refractory disease 100 % (n=10) 4 91 % (n=11) 5 9p24.1 amplification 26 % (n=23) 3 40 % (n=10) 4 PD-L1; programmed death ligand 1, IHC; Immunohistochemistry 1 Paydas et al, 2015; 2 Chen et al, 2013; 3 Green et al; 2010; 4 Ansell et al, 2015; 5 Armand et al, 2015; 6 Koh et al, 2015
Anti-PD1 antibodies in classical Hodgkin lymphoma Number of patients -prior ASCT -prior Brentuximab vedotin Overall response rate -complete response -partial response Nivolumab 1 Pembrolizumab 2 23 18 18 87 % 17 % 70 % 31 22 31 65 % 16% 48% PFS at 24 weeks 86 % 69 % Patients with subsequent Tx -Allogeneic Tx -Autologous Tx Discontinued due to toxicicty 2 (pancreatitis grade 3 and MDS) 6 5 1 ASCT; autologous stem cell transplantation; PFS; Progression free survival, Tx; Transplantation, MDS; Myelodysplastic syndrome 3 2 1 Ansell et al, 2015; 2 Armand et al, 2015
Case presentation KKT Male, born 1997, previously healthy April 2012: Sternal tumor, erroneously diagnosed as LCH, treated with Vinblastine and steroids April 2013: Progressive lesion in the sternum, rebiopsied, now chl, stage IIBEX Treatment according to protocol Euronet-PHL-C1 2 OEPA, interim PET-CT positive, 4 COPDAC, progression prior to planned RT IEP and ABVD, progression 3 courses of brentuximab vedotin, no change 2 courses of IGEV, no change 2 courses of DHAP, radiological partial remission but still PET-CT positive High dose treatment (BEAM), ASCT and involved field RT to 30(36) Gy LCH; Langerhans cell histiocytosis, OEPA; Vincristine, Etoposide, Prednisolone, Doxorubicin, COPDAC; Cyclophosphamide, Vincristine, Prednisolone, Dacarbazine, IEP; Ifosfamide, Etoposide, Prednisolone, ABVD; Doxorubicin, Bleomycin, Vinblastine, Dacarbazine, IGEV; Ifosfamide, Gemcitabine, Vinorelbine, DHAP; Dexamethasone, AraC, Cisplatin, BEAM; BCNU, Etoposide, AraC, Melphalan, ASCT; autologous stem cell transplantation; RT; Radiotherapy, chl; Classical Hodgkin lymphoma
Case presentation KKT February 2015: Progression in the mediastinum, sternum and lungs Rebiopised with findings of chl (CD30 positive) 6 courses of brentuximab vedotin and bendamustin, radiological partial remission but PET-CT positive disease. Not accepted for allogeneic Tx, matched unrelated donor identified. chl; Classical Hodgkin lymphoma, Tx; Transplantation
Case presentation KKT July 2015: Accepted for Keynote 87 (MK-3475-087-00). At start: Palpable tumor upper stenal end, shortness of breath when exercising. Near normal blood test, DLCO 58% of predicted value. 4 courses of pembrolizumab iv, 200 mg, q3w Uneventful, no relevant toxicity. Response assessment at week 12. DLCO; diffusing capacity or transfer factor of the lung for carbon monoxide
Response assessment week 12 KKT Baseline Week 12
Case presentation KKT 3 further courses of pembrolizumab Uneventful, no serious adverse effects, no signs of IRP, weight loss of 10 %. Scheduled response assessment at week 20
Response assessment week 20 KKT Week 12 Week 20
Allogeneic transplant after PD-1 inhibition? CONTRA PRO increased toxicity after PD-1 inhibition? lasting remissions after PD-1 inhibition? no biomaker to predict long term outcome proven curative option best results for patients in remission no salvage option in case of progression intensified GVHD prophylaxis? GVHD; Graft versus host disease Armand et al, 2015
Experience with pembrolizumab in Hodgkin lymphoma KKT MKT C-R Age (years)/sex 18/male 32/female 39/female Failed ASCT and Brentuximab vedotin yes yes yes Number of cycles 7 5 1 Toxicity grade 2-5 no no - Response at 12/20 weeks CR?/CR PR (residual FDG uptake in spleen) Allogeneic Tx planned yes no yes? ASCT; autologous stem cell transplantation; FDG; Fluoro-Desoxy-Glucose, CR; Complete response; PR; Partial response, Tx; Transplantation -