Nivolumab, an anti-PD1, induced Pneumonitis ABDULLAH Jinan (medical - - PowerPoint PPT Presentation

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Nivolumab, an anti-PD1, induced Pneumonitis ABDULLAH Jinan (medical - - PowerPoint PPT Presentation

May 12, 2023 147 likes •365 views

Nivolumab, an anti-PD1, induced Pneumonitis ABDULLAH Jinan (medical oncology resident French board) 2016 Mme. Ma.P 55 yrs, female Ex-smoker (35 cig/day) Autonomous Bronchogenic squamous cell carcinome cT4N3M0 in Feb 2012 6th line:

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Nivolumab, an anti-PD1, induced Pneumonitis

ABDULLAH Jinan (medical oncology resident French board) 2016

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  • Mme. Ma.P

55 yrs, female Ex-smoker (35 cig/day) Autonomous Bronchogenic squamous cell carcinome cT4N3M0 in Feb 2012

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6th line: Immunotherapy! ☺ Anti-PD1 Nivolumab (6ème ligne) Aug 2015

I.V. 3mg/KG over 60mins, every 2 weeks Regression after 2 courses

http://www.webmd.com/drugs/2/drug-167497/nivolumab-intravenous/details

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Dendritic cell Healthy cell Unhealthy cell T-cell

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After 7th course: Right basal pneumonia, admitted for 2d, treated with 10d Augmentin.

Before

After ☺

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9th course Nivolumab: 12th April 2016 15th April: SAMU: fever, cough, cyanosis GCS 13-14/15 RR: 28br/min BP: 90/60 SpO2: 67%, increase to 95% with 9L/min O2 Clinical exam: right basal crepitation ECG: normale sinus rythme, incomplete BBB CRP 88, PCT 0.41

ICU Admission

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CRP increases to 156mg/l

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Differential diagnosis???

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Tazocillin et Amikacin (recently treated with Augmentin, considered nosocomial infection) Rigid BAL: H.influenza, switch to ceftriaxone (7d totale) CRP decreases (156 vs 76) 2nd BAL: sterile

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  • BiPAP doesn’t work..
  • Intubate with noreadrenaline.

She is not getting better…

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  • Systemic steroids…
  • Deterioration…
  • Passes away: 27/04
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Anti-PD1 induced pneumonitis

  • Diagnosis of exclusion
  • NEJM Phase1 in July 2015:

–3 cases in phase 1 trial due to anti-PD1 related pneumonitis (out of how many?)

  • Grading using the CTCAE system
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Grade 1: asymptomatic pneumonitis with radiological changes withhold drug, monitor every 2-3d, CT scan in 3 wks Grade 2: symptomatic. Non-invasive tx. Withhold drug until. prednisone 0,5mg/KG/Dday or equivalent if symptomes >1week Grade 3-4: Severe symptomes/life-threatening. Discontinue drug Prednisone 1-2mg/KG/day. Taper when grade1 No improvement in 3days??? 2nd line Infliximab (5mg/kg max X2 interval 2 weeks) once infection excluded, rather than long-term high-dose steroids

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What does the literature say?

  • NEJM, Mizuki Nishino, MD, Woman's Hospital in Boston,

Massachusetts, July 2016 : 3 cases pneumonitis (out of how many?) : 2 ICU. 1 died. (some had ipilumumab)

  • NEJM Sept 2015; checkmate 057: phase 3 trial Nivolumab vs

Docetaxel in NSCLC: pneumonitis 3% Nivolumab <1%

  • docetaxel. D/C drug
  • American Association Thoracic Surgery: Pneumonitis with

nivolumab treatment shows common radiographic patterns , Sept 2016: 20 pts pneumonitis tx with steroids +/- infliximab. 17 restarted Nivolumab, 2 recurrent pneumonitis

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Take home message: Respiratory examination+ low threshold for imagery in Nivolumab

Thank you ☺ Jinan Abdullah