eventi avversi immuno-correlati: caso...
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Laura BonannoOncologia Medica 2
Istituto Oncologico Veneto IRCCS
Eventi avversiimmuno-correlati:
Caso clinico
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Wang et al, JAMA Oncol 2019
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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
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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)
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Sept 2016 Nov 2016Aug 2016
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- Previous RT (6 months before)- Previous bacterial pulmonary infection- Currently asymptomatic
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Differential diagnosis1- consider progressive disease
2- infectious origin/complications
3- consider timing, comorbidities, kind of neoplasm, kind of ICI, previous treatment….
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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
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PNEUMONITIS:ESMO-ASCO
Haanen JBAG et al, Ann Oncol 2017
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DELAY, OBSERVE AND FURTHER STUDY(monitoring infection)
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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)
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START STEROIDS Add voriconazoleCareful clinical monitoring
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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
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TREATMENT RE-ADMINISTRATION?
Available data
on discontinuation
and efficacy
Intent of treatment
and disease
Response
Right steroid administration
Monitoring feasibilityRisks:
Kind of tox
comorbidities
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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
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Readministration and toxicity
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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
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PLR AT AE AND RISK OF
RELAPSE/SECOND AE
Pavan A et al, ESMO 2019
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Bonanno L et al, JTO 2019
NOV 2019Treatment Ongoing
NOV 2019Treatment Ongoing
STOP PER PROTOCOL
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Bonanno L et al, JTO 2019
PANCREATIC RT FOR OLIGOPD
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SYNERGY FOR RADIATION AND IMMUNE RESPONSE
Crittenden, ASCO 2018
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Champiat S. et al, Annals of Oncology 2015
TREATMENT:Not only steroids!