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Immunotherapy: Guilty?

Ana Cardeña Gutiérrez

H. Universitario Fundación Alcorcón (Spain).

Medical Oncology

Immuno-Oncology– Zurich– 10-11 May 2019

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DISCLOSURE OF INTEREST

� None. I declare that there are no financial conflicts of interest with

regard to this work.

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Clinical case (I)

Mr MC was born in 1950.

� Medical history: Current smoker,

moderate COPD, AF anticoagulated with

acenocumarol, TIA secondary to right

MCA stenosis (November-12).

� Oncological history:

– Nov-12: Epidermoid carcinoma of

the lung IIIA (cT2N2M0)-7thed AJJC-

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He received:

– Neoadyuvant treatment: Paclitaxel + Carboplatin x4: Partial

response.

– Concomital chemoradiotherapy (66 Gy): Stable disease. End

in Jul-13.

– 1st line palliative chemotherapy: Gemcitabine + Carboplatin

x3. Progression. PFS 3m.

– 2nd line: Vinorelbine x3. Partial response but grade 3 toxicity.

Monitoring until mediastinal progression (Mar-14)�PFS 11m

Monitoring until mediastinal progression (Apr-15)�PFS 11m

Clinical case (II)

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Clinical case (III)

– Nivolumab 3 mg/kg/2w since Jun-15 (expanded use). Stabledisease. Grade 1 hypothyroidism and asthenia.

Sep-16: Acute symmetrical paraparesis.

CT, MRI:

Electromyogram: Mixed Axonal Polyneuropathy with demyelinatingfeatures.

Albumin: 1,3 g/dl (3,5-5,2)

Ig G: 407 mg/dl (690-1400)

Glu 252 mg/dl (40-70)

Protein level: 36,7 mg/dl (15-40)

Lactate: 4,2 mmol/l (0-3)

Leucocytes: 1 cel/mm3

No oligoclonal bands

Gram stain and culture negative.

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Neurological immune mediated adverse events (nRAEs)

� Real life incidence is variable between series but is considered a rare

adverse event.

� They usually appear after 5-6 weeks of treatment.

� Peripheral neuropathy, Guillain-Barre-like syndromes, cranial nerve

palsies, demyelination and myasthenia gravis-type syndromes are all

recognised adverse effects.

� The best approach to nRAEs management is not defined. Generally

the majority of them can be effectively reversed with corticosteroid,

and alternative treatments such as IV Ig and plasmapheresis may

need to be employed in situations with an antibody-mediated

pathogenesis.

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� Diagnosis: Late onset Guillain-Barré-like syndrome -after 23 cycles of

nivolumab-.

� Treatment: Corticoesteroids 1 mg/kg/day iv for 2 weeks. Slow

descending dose planned for a month (oral administration).

– Glycemic decompensation.

– Steroid myopathy.

– Predisposition to infections.

Clinical case (IV)

Dec-16: Bacteremic Biliary Tract Infection.He died 2 weeks after admission becauseof sepsis, with stable disease.

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Conclusions

� We found a late onset and rare adverse event with nivolumab with

corticosteroid response. Our patient died but not because of tumor

progression or immunomediated toxicity, rather he mostly suffered

from the treatment’s secondary complications.

� In the future, we should consider researching not only early diagnosis

for immune related adverse events, but also its optimal management

and support treatment for patients.

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Thank for your attention