Impact sur le profil patient en ranimation Michael Darmon Service - - PowerPoint PPT Presentation

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Impact sur le profil patient en ranimation Michael Darmon Service - - PowerPoint PPT Presentation

Dec 17, 2022 49 likes •383 views

Ranimation au temps des CAR-T Cells : Impact sur le profil patient en ranimation Michael Darmon Service de ranimation mdicale CHU Saint-Louis Universit Paris 7 Conflits dintrts Research grants: MSD, Astute medical

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Réanimation au temps des CAR-T Cells : Impact sur le profil patient en réanimation

Michael Darmon Service de réanimation médicale CHU Saint-Louis Université Paris 7

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Conflits d’intérêts

▪ Research grants: MSD, Astute medical ▪ Speaker fees: MSD, Astellas, Bristol Myers Squibb, Gilead ▪ Support in organizing educational meetings: MSD, Astellas, JazzPharma ▪ Advisory board: Sanofi Aventis, Gilead-Kite

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CAR-T: a potential « game changer »

Neelatu et al. N Engl J Med 2017; Haartman et al. EMBO 2017

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CAR-T: A limited experience

Haartman et al. EMBO 2017

2017: ~ 400 CAR-T patients reported 2/3 with anti-CD19 CAR-T

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CAR-T: an exponential progression

Haartman et al. EMBO 2017

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CAR-T Cells recipients and ICU

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Half CAR-T Cells recipients will require ICU

Hay et al. Blood 2017

  • CAR-T Anti-CD19
  • 133 patients (47 ALL, 24 CLL, 62 NHL)

Stage 2+ sepsis ICU Admission

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Half CAR-T Cells recipients will require ICU

Hay et al. Blood 2017

  • Early CRS = severe CRS
  • Severe CRS = Neuro toxicity
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Expect CRS but assume Sepsis

Hill et al. Blood 2018

  • Cumulative rate of infection ~40-50%
  • High rate of viral and fungal infection

Adjusted ratio of infection density ALL>CLL>LNH (Ratio 2.7 and 4.4) Prior regimen >4 (Ratio 3,5) Dose >2*107 (Ratio >7)

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Expect CRS but assume Sepsis

Hill et al. Blood 2018

  • No reporting of adjusted risk (collinearity)
  • Risk factors as usual in high risk patients

CAR-T cells dose Neutropenia Severity

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Expect CRS but assume Sepsis

Hill et al. Blood 2018

  • Some patients misleadingly classified as “CRS”
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Expect CRS but assume Sepsis

Hill et al. Blood 2018

  • Some patients misleadingly classified as “CRS”

42% 30% 13% 8% 6% 10% 6%

Any infection Bacterial Including BSI Fungal Including mold Viruses Including RV

Rate

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CAR-T cells as source of MOF

Brudno et al. Blood 2018

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How to prepare for CAR-T in ICU

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Anticipation of ICU admission

SOP Saint-Louis

  • ICU team is informed of every CAR-T infusion
  • ICU involved in older potential recipients / Comorbid patients
  • Grade 2 CRS/NT requires ICU admission
  • Grade 2 CRS/NT should be treated as sepsis
  • Specific therapies (Anti-IL6/Steroids) are validated collegially
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Identification of high risk patients

Hay et al. Blood 2017

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Early fever or high fever= severe CRS

Hay et al. Blood 2017

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Early ICU Admission

Hourmant et al. Soumis

  • General population of Critically Ill Cancer Patients
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Early ICU Admission

Thiery et al. J Clin Oncol 2007

  • Poor reliability of severity assessment, increased mortality of late admission

0.2 0.4 0.6 0.8 1 5 10 15 20 25 30

Days

Lack of severity mortality 8.5% ICU admission mortality 45.7% Futility Mortality 75% late ICU admission mortality 61.5%

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Multidisciplinary round is the rule

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Pitfalls

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Beware limits of current CRS staging

Porter et al. J Hematol Oncol 2018

  • Example: CTCAE definition of AKI less stringent than consensus definition
  • CTCAE kidney dysfunction stage 2 = severe AKI (KDIGO stage 3)
  • To reach AKI stage 1 (+26μmol sCreat or +50%):
  • 5 to 10 hours with > 40% decrease in GFR
  • AKI stage 1 = +50% short term mortality
  • AKI stage 1 = increased risk in readmission, long term mortality, and CKD
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Saint-Louis University Hospital

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Our experience

33 CAR-T 60% NHL ICU admission n=13 (40%) 5 Neuro T (36%) including 3 NT grade 3/4 5 with concurrent CRS (100%) 12 CRS 2+ (93%) Including 4 CRS 3-5 4 Sepsis 2 with microbio doc.

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Our experience

  • ALL-B = 9 Pts/13
  • Anti-IL6 systematically required
  • Steroids required in 2/3 of ICU CAR-T patients
  • Confirmed sepsis in 1/3 of ICU CAR-T patients
  • Septic patients may reach apyrexia after Toci
  • 2 early deaths (<15 days)
  • 4 Early failures
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Take home message

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Before CAR-T

  • Be available for trials kick-off / institution selection
  • Assessing performance status
  • Assessing overall risk of ICU admission
  • Introducing ICU team to the patients and their next of kin
  • According to institution processes
  • Monitoring during apheresis
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Day of CAR-T infusion

  • Be available
  • Record day of infusion / anticipate ICU admission
  • Early evaluation by outreach team if fever
  • Early ICU admission
  • High risk patients
  • Early CRS + minimal organ dysfunction
  • CRS stage 2 or more: Assume sepsis and ICU admission
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After ICU admission

  • Antibiotics systematically
  • Antifungal therapy if needed
  • Anti-IL6 if CRS
  • Steroids : severe CRS and Neurotoxicity
  • Multidisciplinary rounds
  • Adjust according to trials
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Conclusion

  • Potential game changer
  • A high number of potential recipients
  • A high rate of ICU admission
  • A high rate of sepsis to be expected
  • CRS stage 2: 50% chances of infection
  • Early ICU admission since predicting ”clinical worsening” is unreliable
  • Multidisciplinary rounds because we care for our patients
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Merci de votre attention