Laura BonannoOncologia Medica 2

Istituto Oncologico Veneto IRCCS

Eventi avversiimmuno-correlati:

Caso clinico

Wang et al, JAMA Oncol 2019

68 year old manHeavy smokersNo relevant comorbiditiesPS ECOG 1

Diagnosis of small-cell lung cancerStage pT2aN2Staging: brain thorax abdomen CT scan+bone scan

multidisciplinary evaluation

Cisplatin-etoposide x 3 PRRadical-intent radiotherapy PRPCI

PROGRESSIVE DISEASE

LD ED

1983 2015 1983 2015

Median Survival (months) 14 18-24 7 9-10

3-years Survival (%) 15-20 0

5-years Survival (%) 20-25 0-5

Nivolumab single-agent (3 mg/kg)

Sept 2016 Nov 2016Aug 2016

- Previous RT (6 months before)- Previous bacterial pulmonary infection- Currently asymptomatic

Differential diagnosis1- consider progressive disease

2- infectious origin/complications

3- consider timing, comorbidities, kind of neoplasm, kind of ICI, previous treatment….

Suspected immunorelated toxicity

Grade 1

Radiographic

changes only

• Consider delay of I-Therapy

• Monitor symptoms every 2–3 days

Re-image at least q3wIf worsens: treat as grade 2–4

DELAY AND OBSERVE

PNEUMONITIS:ESMO-ASCO

Haanen JBAG et al, Ann Oncol 2017

DELAY, OBSERVE AND FURTHER STUDY(monitoring infection)

BRONCHOSCOPY (AND LUNG BIOPSY):

ASPERGILLUS

CT-SCAN:

WORSENING OF POTENTIALLY IMMUNORELATED ASPECTS

MULTIDISCIPLINARY DISCUSSION:- NO SYMPTOMS

- NO RADIOLOGICAL LESIONSTYPICAL FOR ASPERGILLUS(and other exams: fundus onculi,AG, repeat bronchoscopy)

START STEROIDS Add voriconazoleCareful clinical monitoring

AFTER RESOLUTION

GRADUAL STEROID TAPERING

At least 4-6 weeks

Temporary suspension Permanent discontinuation

- IrAEs stabilized < G1- Steroid dose reduced to <

10 mg/d prednisone

- IrAEs G4- IrAEs G3 and recurring- IrAEs G2 not resolutive in

3 months

TREATMENT RE-ADMINISTRATION?

Available data

on discontinuation

and efficacy

Intent of treatment

and disease

Response

Right steroid administration

Monitoring feasibilityRisks:

Kind of tox

comorbidities

Discontinuation and efficacy

Jansen et al, Ann Oncol 2019

Median time on treatment: 12 mMedian follow-up after discontinuation: 18 mMedian time to PD: 12 m18 m: 78% non-PD

Readministration and toxicity

Elements affecting irAEPatient: non-pathological immune-related factors-BASELINE

Pavan A et al, Oncologist 2019

Univariate Multivariate

IrAE/N % OR 95%CI p-value OR 95%CI p-value

L-NLR 32/74 43.2% 2.2 1.1-4.1 0.018 1.7 0.8-3.3 0.160

H-NLR 26/100 26.0% 1 1

L-PLR 42/98 42.9% 2.8 1.4-5.5 0.003 2.3 1.1-4.8 0.027

H-PLR 16/75 21.3% 1 1

PLR AT AE AND RISK OF

RELAPSE/SECOND AE

Pavan A et al, ESMO 2019

Bonanno L et al, JTO 2019

NOV 2019Treatment Ongoing

NOV 2019Treatment Ongoing

STOP PER PROTOCOL

Bonanno L et al, JTO 2019

PANCREATIC RT FOR OLIGOPD

SYNERGY FOR RADIATION AND IMMUNE RESPONSE

Crittenden, ASCO 2018

Champiat S. et al, Annals of Oncology 2015

TREATMENT:Not only steroids!