NEOADJUVANT IMMUNOTHERAPY IN MELANOMA

NEOADJUVANT IMMUNOTHERAPY IN MELANOMA

The pathway towards personalised immunotherapy

Christian Blank The Netherlands Cancer Institute, Amsterdam

TARGETED THERAPY AND IMMUNOTHERAPY HAVE IMPROVED

3 year OS of stage IV melanoma patients

58%

50%*

52%

44%

37%

31%

32%

20%

12%

DTIC

Ipilimumab Vemurafenib Dabrafenib Vemurafenib Dabrafenib Pembrolizumab Nivolumab

Ipilimumab

+ Cobimetinib + Trametinib

+ nivolumab

*OS rate at 33 months

Hodi FS, et al. NEJM 2010; Robert C, et al. NEJM 2011; COMBI-d ASCO 2016; COMBI-v ESMO 2016; Co-BRIM - SMR 2016, Keynote 006 - ASCO 2017; Larkin J, et al. NEJM 2019

ONLY A SUBGROUP OF PATIENTS BENEFITS LONG-TERM FROM THE CURRENT THERAPIES...

...and not all need a toxic combination therapy ? urgent need for personalisation of immunotherapies

From N Engl J Med, Larkin J, et al. Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma, 381, 1535-1546.Copyright ? (2019) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.

MULTIPARAMETER BIOMARKERS ARE KEY

The Cancer Immunogram

Tumor foreignness Mutational load

Tumor sensitivity to immune effectors MHC expression IFN-g sensitivity

General immune status Lymphocyte count

Absence of inhibitory tumor metabolism

LDH, glucose utilization

Absence of soluble inhibitors IL6->CRP/ESR

From Blank CU, et al. Science 2016, 352(6286): 658-660. Reprinted with permission from AAAS.

Immune cell infiltration Intratumoral T cells

Absence of Checkpoints PD-L1

WHICH PATIENTS ALWAYS HAVE A FAVOURABLE CANCER IMMUNOGRAM?

Tumor foreignness Mutational load

Tumor sensitivity to immune effectors MHC expression IFN-g sensitivity

General immune status Lymphocyte count

Absence of inhibitory tumor metabolism

LDH, glucose utilization

Absence of soluble inhibitors IL6->CRP/ESR

From Blank CU, et al. Science 2016, 352(6286): 658-660. Reprinted with permission from AAAS.

Immune cell infiltration Intratumoral T cells

Absence of Checkpoints PD-L1

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