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

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: Immunotherapy! ☺ Anti-PD1 Nivolumab (6 ème 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

Dendritic cell Healthy cell Unhealthy cell T-cell

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

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

CRP increases to 156mg/l

Differential diagnosis???

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

• BiPAP doesn’t work.. • Intubate with noreadrenaline. She is not getting better…

• Systemic steroids… • Deterioration… • Passes away: 27/04

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

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??? 2 nd line Infliximab (5mg/kg max X2 interval 2 weeks) once infection excluded, rather than long-term high-dose steroids

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

Take home message: Respiratory examination+ low threshold for imagery in Nivolumab Thank you ☺ Jinan Abdullah