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