DERMATOLOGIST, MOHS SURGEON CHUGLD, MONCTON NB Disclosures / - - PowerPoint PPT Presentation

DR MARTIN LEBLANC MD FRCPC FCDA DERMATOLOGIST, MOHS SURGEON CHUGLD, MONCTON NB

Disclosures / Conflicts of interest

▪Honorariums : ▪AbbVie ▪Sanofi-Genzyme Canada ▪LEO

Objectives :

▪ Overview of the cutaneous adverse effects of immunotherapy ▪Is there a survival benefit for patients receiving immunotherapy in the advent of these cutaneous advserse events

Overview of the cutaneous adverse effects

• f immunotherapy

▪Classification...

Overview of the cutaneous adverse effects

• f immunotherapy

▪Enumeration !

▪ Morbilliform eruption ▪ Eczema like (spongiotic dermatitis) ▪ Pruritus ▪ Lichenoid eruption ▪ Psoriasis or psoriasiform eruption ▪ Acneiform ▪ Vitiliginous ▪ Hypersensitivity syndrome : DRESS ▪ Auto-immune (Bullous, dermatomyositis, Alopecia areata) ▪ Other (sarcoidosis, nail, oral mucosal changes)

Overview of the cutaneous adverse effects

• f immunotherapy

▪Morbilliform eruption

▪Aka ‘Maculopapular eruption’ ▪The most frequent ▪CTLA4 inh (1/4pts) > PD-1 (1/6pts)

▪** PD-L1 preliminary data 1/10pts

▪Rate of grade 3, less than 3%

Overview of the cutaneous adverse effects

• f immunotherapy

▪Morbilliform eruption – Management:

▪Mid to high potency topical steroid :

▪(Betamethasone valerate – 450g!)

▪+/- anti-histamine ▪Systemic steroid – case by case

▪If so, hold immunotherapy and restart once <10mg/day ▪Does not interfere with anticancer immune response

Overview of the cutaneous adverse effects

• f immunotherapy

▪Lichenoid eruption

▪More violaceous ▪Later onset ▪Intensly pruritic

Overview of the cutaneous adverse effects

• f immunotherapy

▪Psoriasis

▪Better delineated ▪Key areas (extensory, nails..) ▪Arthritis

Overview of the cutaneous adverse effects

• f immunotherapy

▪Life threatening

▪Stevens-Johnson ▪TEN (toxic epidermal necrolysis) ▪DRESS ▪Other (Vasculitis, Sweet syndrome, Bullous pemphigoid)

SJS-TEN

DRESS – Drug rash with eosinophilia and systemic symptoms

▪Often morbilliform presentation plus…

▪ Fever ▪ Swelling (face)! ▪ Adenopathy ▪ Eosinophilia ▪ Hepatitis ▪ Nephritis ▪ Pneumonitis ▪ Etc…

Objective #2 :

▪Is there a survival benefit for patients receiving immunotherapy in the advent of these cutaneous advserse events ?

Preamble :

Is there a survival benefit for patients receiving immunotherapy in the advent of these cutaneous advserse events

Australian study – Westmead hospital

Method

▪Prospective cohort study, stage IIIC/IV

melanoma pt tx Pembrolizumab or Nivolumab ▪May 1st 2012 → Feb 1st 2018 ▪Tumor response evaluated using ir-RECIST

▪82 pts (5 Nivolumab, 77 Pembrolizumab)

▪Median follow up = 40 months ▪33 pts who developed at least one target skin reaction (TSR) = Eczema, Lichenoid, vitiligo-like

Method

▪Analysis

▪Cox proportional hazards model with time dependent covariates to assess the association between the development of the CAE and disease progression or death ▪Landmark studies

Method

▪Results

▪Primary analysis : time-dependent Cox proportional hard model for disease progression/death

▪ At any point in time on tx with PD-1, individuals who had

• ne or more CAE had a 54% less instantaneous risks of

experiencing progressive disease/death who had not developed any reaction by this time

▪ Hazard ratio 0.46 with 95% CI (0.23-0.91) p=0.025

▪Results

▪Landmark analyses at 6 and 12 months

▪6 months = 50% less risk of disease progression/death ▪12 months= 66% less risk of disease progression/death

▪Limitation

▪Low sample size ▪Only studied the univariate association between the development

• f one or more CAE and disease progression/death

▪Landmark time reduces the event rate within this population

Take away

▪Morbilliform eruption

▪look for any criteria of severity (mucous membrane involvment, Nikolsky sign, purpura, palmarplantar...) ▪Usually self-limiting and manageable ▪Combination ICI = more frequent, severe and earlier cutaneous irAE

Take away

▪The relation between cutaneous adverse events and impact on final outcome

▪Interesting surrogate marker

References :

▪ The oncological survival and prognosis of individuals receiving PD-1 inhibitor with and without immunologic cutaneous adverse events, J Am Acad

• Dermatol. 2019 Jun 21. pii: S0190-9622(19)31024-2. doi: 10.1016/j.jaad.2019.06.035

▪ Dermatologic Reactions to Immune Checkpoint Inhibitors, American Journal of Clinical Dermatology, June 2018, Volume 19, Issue 3, pp 345–361 ▪ Bullous Lupus Under Nivolumab Treatment for Lung Cancer: A Case Report With Systematic Literature Review. Anticancer Res. 2019 Jun;39(6):3003-

• 3008. doi: 10.21873/anticanres.13432.

▪ Anticancer Res. 2019 Jun;39(6):3003-3008. doi: 10.21873/anticanres.13432. Dermatol Clin. 2019 Oct;37(4):555-568. doi: 10.1016/j.det.2019.05.013. Epub 2019 Jul 27. ▪ Nivolumab-induced lichen planus. J Oncol Pharm Pract. 2019 Aug 5:1078155219866248. doi: 10.1177/1078155219866248 ▪ Diverse cutaneous adverse eruptions caused by anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) immunotherapies: clinical features and management, Ther Adv Med Oncol. 2018; 10: 1758834017751634. ▪ BOLOGNIA and al. Dermatology, 3rd Edition, 2012 ▪ FITZPATRICK’s, Dermatology in general medicine, 8th edition, 2012. ▪ Up to Date ▪ Pubmed

Thank you, Questions?