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Immune checkpoints inhibitors, toxicity and outcome:

a case report

Teresa Beninato – Istituto Nazionale Tumori (Milano)

Immunoncology– Zurigo – 09/05/2019

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DISCLOSURE OF INTEREST

� The author declare that she has no conflict of

interest

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Background

� Male, 78 years old, ECOG PS1

� Hypertension, Diabetes Mellitus

� Diagnosed with advanced lung adenocarcinoma

� First line therapy with Pembrolizumab 200 mg flatdose d1 q21

EGFR wt, ALK and ROS1 not rearranged,

PD-L1: TPS >50%

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G4 muscular toxicity

Two weeks after starting Pembrolizumab:

Access to the Emergency Room for dyspnoea and generalized muscularhypostenia

� Arterial Blood Gas (ABG) : pH 7.35, pO2 52 mmHg, pCO2 52 mmHg

� Laboratory assessments: CPK 7175 ng / mL, CK MB 156 IU / L, Troponin T 1630 ng / ml

Rapid worsening of the respiratory failure and ABG

� CT angiography: negative for pulmonary embolism

� Echocardiography: marked septal asynchrony and infero-lateral hypo-acinesia

� Electromyography: myopathic involvement of the diaphragm

Transfer in Intensive Care Unit

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Management

Emergency management

� Tracheostomy, invasive mechanical ventilation

� High dose steroid therapy: methylprednisolone 2 mgkg IV

� Intravenous immunoglobulins (IVIG)

� Complete recovery of peripheral myopathy, partial recovery of diaphragmatic myopathy

Permanent discontinuation of immunotherapy

� No other active cancer treatments started

Eight months later…

� Impressive clinical improvement with removal of thracheostomy

� Restaging CT scan: Complete Responce after a single dose of Pembrolizumab

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Potential predictive role of irAEs

� Vitiligo & tumor response association demonstrated in

melanoma

� Increasing evidence in NSCLC:

– Skin toxicity & tumor response

– Thyroiditis & OS

– Early toxicities & OS, PFS and ORR

[Hua C et al, JAMA Dermatol 2016]

[Hasan Ali O, et al. Oncoimmunology 2016]

[Osorio JC. Et al. Ann Oncol 2016]

[Haratani K et al. JAMA Oncol 2018]

[Teraoka et al. J Tor Oncol 2017]

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Thank you for your attention