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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 : Honoraria
• Roche: Honoraria and research support
Lymphoblasticlymphoma
1 %
Periperal T-cell lymphoma
6 %
Anaplastic large celllymphoma
2 %
Follicularlymphoma
22 %
Mantel cell lymphoma6 %
Marginal zonelymphoma
5 %
Lymphocytic lymphoma6 %
Diffuse large B-cell lymphoma31 %
Burkitt lymphoma2 %
Hodgkin lymphoma14 %
WHO for dummies…
Lymphoplasmacyticlymphoma
1%
Courtesy of J. Delabie
WHO; World Health Organisation
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
CD3
CD30
Classical Hodgkin lymphoma -microenvironment
Courtesy of S. Spetalen; Küppers et al., 2012
PD-L1 in Classical Hodgkin lymphoma
Primary disease Relapsed/refractory disease
PD-L1 expression (IHC) 21 % (n=87)1
87 % (n=38)2
75 % (n=109)6
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; 2Chen et al, 2013; 3 Green et al; 2010; 4 Ansell et al, 2015; 5 Armand et al, 2015; 6Koh et al, 2015
Anti-PD1 antibodies in classical Hodgkin lymphoma
Nivolumab1 Pembrolizumab2
Number of patients-prior ASCT-prior Brentuximab vedotin
231818
312231
Overall response rate-complete response-partial response
87 %17 %70 %
65 %16%48%
PFS at 24 weeks 86 % 69 %
Patients with subsequent Tx-Allogeneic Tx-Autologous Tx
651
3
Discontinued due to toxicicty 2 (pancreatitis grade 3
and MDS)
2
ASCT; autologous stem cell transplantation; PFS; Progression free survival, Tx; Transplantation, MDS; Myelodysplastic syndrome
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
• 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.
Case presentation KKT
cHL; Classical Hodgkin lymphoma, Tx; Transplantation
• 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.
Case presentation KKT
DLCO; diffusing capacity or transfer factor of the lung for carbon monoxide
Response assessment week 12 KKT
Baseline
Week 12
• 3 further courses of pembrolizumab
• Uneventful, no serious adverse effects, no signs of IRP, weight loss of ≈ 10 %.
• Scheduled response assessment at week 20
Case presentation KKT
Response assessment week 20 KKT Week 12
Week 20
•proven curative option•best results for patients in remission•no salvage option in case of progression•intensified GVHD prophylaxis?
•increased toxicity after PD-1 inhibition?•lasting remissions after PD-1 inhibition?•no biomaker to predict long term outcome
PROCONTRA
Allogeneic transplant after PD-1 inhibition?
GVHD; Graft versus host disease
Armand et al, 2015
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 FDGuptake in spleen)
-
Allogeneic Tx planned yes no yes?
Experience with pembrolizumab in Hodgkin lymphoma
ASCT; autologous stem cell transplantation; FDG; Fluoro-Desoxy-Glucose, CR; Complete response; PR; Partial response, Tx; Transplantation