CAR-T 細胞治療

Buzzwords → Dx

Diagnostic Criteria — Toxicities (ASTCT consensus)

CRS Grading:

• Grade 1: Fever ≥38 °C without hypotension or hypoxia.
• Grade 2: + hypotension responsive to fluids OR low-dose vasopressors OR hypoxia O₂ <40 %.
• Grade 3: + hypotension on multiple/high-dose vasopressors OR hypoxia O₂ ≥40 %.
• Grade 4: Life-threatening; multiple vasopressors + mechanical ventilation.

ICANS Grading (ICE score 0-10):

• Grade 1: ICE 7-9.
• Grade 2: ICE 3-6.
• Grade 3: ICE 0-2 OR seizures responsive OR focal edema on imaging.
• Grade 4: Unable to perform ICE (coma) OR life-threatening seizures OR cerebral edema.

Workup pre-CAR-T

• Disease assessment + cardiac (EF, QTc), pulmonary, neuro baseline (ICE).
• Active infection / hepatitis B/C/HIV screening.
• Brain MRI if neuro history.
• Bridging therapy plan (pola-R-bendamustine, ICE, GDP for B-NHL; PROLI for MM; AVOID bendamustine within 100 d before leukapheresis — depletes T cells).
• Lymphodepleting chemo (Flu-Cy) typically 3 d before CAR-T infusion.

Treatment Algorithm (post-infusion)

flowchart TD
  A[CAR-T infused day 0] --> B[Monitor q1-2 h × 7 d<br>vitals, neuro exam ICE score]
  B --> C{Symptoms?}
  C -- fever only<br>grade 1 CRS --> D[Acetaminophen + supportive<br>infectious workup<br>tocilizumab early if persistent]
  C -- hypotension hypoxia<br>grade 2-3 CRS --> E[TOCILIZUMAB 8 mg/kg<br>± dexamethasone<br>vasopressors / O₂]
  C -- grade 4 CRS --> F[Tocilizumab + high-dose dex<br>± anakinra<br>ICU + vasopressors + intubation]
  C -- ICANS --> G[DEXAMETHASONE<br>NOT tocilizumab — doesn't cross BBB<br>methylpred for grade 3-4]
  G --> H{Seizures?}
  H -- yes --> I[Levetiracetam<br>EEG monitoring]
  C -- HLH-like / refractory --> J[Anakinra<br>± etoposide<br>IL-1 / JAK pathway blockade]
  B --> K[Long-term: monitor cytopenias × months<br>BCMA CAR-T → hypogamma → IVIG<br>infection ppx PJP/HSV/VZV/antifungal]

Pearls / Pitfalls

• Tocilizumab is for CRS, NOT ICANS — it doesn't cross the blood-brain barrier. Picking tocilizumab for confused/aphasic patient is wrong.
• Steroids (dexamethasone) are first-line for ICANS; for CRS, add steroids when tocilizumab insufficient or ICANS develops.
• HOLD bendamustine ≥100 d before leukapheresis — T-cell depleting → poor CAR-T expansion.
• Bridging therapy is critical to control disease in 2–3 wk manufacturing window — pola-R-benda (DLBCL), R-ICE / R-GDP, MM-specific bridges.
• CAR-T-induced cytopenias can be prolonged (weeks to months) — TPO-RAs, G-CSF, transfusions; some need stem cell boost.
• BCMA CAR-T → hypogammaglobulinemia + recurrent infections → IVIG replacement; PJP / HSV / VZV / antifungal prophylaxis.
• Second primary malignancies (SPM) post-CAR-T — FDA boxed warning 2024; T-cell malignancies reported; monitor.
• CD19 antigen loss is a common mechanism of CAR-T resistance → consider CD22 CAR-T (investigational) or alternate strategies.
• Allogeneic CAR-T (off-the-shelf) is investigational; addresses manufacturing delays; risk of GVHD.
• Bispecifics (blinatumomab, teclistamab, epcoritamab, glofitamab, talquetamab) — alternatives to CAR-T; off-the-shelf, monoclonal-like dosing; CRS / ICANS still occur but typically milder.
• Liso-cel CLL approval (TRANSCEND CLL 004) — for R/R CLL post-BTKi + post-Ven.
• TLS at infusion — pre-treat with rasburicase + IVF in high disease burden.
• Tisa-cel for pediatric/AYA ALL age ≤25 yo (ELIANA — high CR + durable remission).

Cross-references

• DLBCL — CAR-T 2L
• ALL — CAR-T relapsed
• CLL — liso-cel TRANSCEND CLL 004
• MM — BCMA CAR-T
• TLS — pre-CAR-T prophylaxis
• Post-CAR-T infection ppx
• Drug Regimens — CAR-T list

相關題目

• Q-002 — DLBCL — second-line therapy for primary-refractory disease
• Q-045 — MCL — relapsed disease post-BTKi
• Q-157 — CAR-T — CRS vs ICANS management
• Q-158 — CAR-T — ICANS management
• Q-159 — CAR-T — bridging therapy and bendamustine timing

Sources