What defines a patient as ineligible for chimeric antigen receptor T‑cell (CAR‑T) therapy, including criteria such as Eastern Cooperative Oncology Group performance status, organ dysfunction (e.g., left ventricular ejection fraction, renal clearance, bilirubin, transaminases), uncontrolled infections, central nervous system disease, autoimmune disease, graft‑versus‑host disease, inability to undergo safe leukapheresis, pregnancy, lactation, hypersensitivity to product components, and age‑related considerations?

Definition of CAR-T Ineligibility

Patients are ineligible for CAR-T therapy if they have poor performance status (ECOG ≥2, Karnofsky ≤60%, or Lansky ≤60%), life expectancy <6-8 weeks, active uncontrolled infections, active grade II-IV acute or extensive chronic graft-versus-host disease, or are on systemic immunosuppression. 1

Performance Status and Life Expectancy

• ECOG performance status ≥2 (or Karnofsky ≤60%, Lansky ≤60%) is a contraindication to CAR-T therapy, as patients with ECOG >1 treated outside clinical trials demonstrated significantly decreased overall survival and progression-free survival. 1
• Life expectancy must exceed 6-8 weeks for CAR-T eligibility, requiring careful risk-benefit assessment in patients with shorter expected survival. 1

Infectious Disease Contraindications

Active infections represent absolute contraindications:

• Active bacterial or fungal infections must be treated and well-controlled before leukapheresis, with patients clinically stable; most cases require only temporary deferral. 1
• Active viremia is a contraindication requiring deferral until infection is controlled. 1
• Latent infections (HIV, HBV, HCV) are contraindications for several (but not all) commercial CAR-T products; when proceeding with latent infections, prophylactic antiviral treatment is mandatory. 1
• Asymptomatic COVID-19 positive patients may proceed at physician's discretion after checking feasibility with the manufacturer. 1

Graft-Versus-Host Disease and Immunosuppression

• Active grade II-IV acute GVHD or extensive chronic GVHD is an absolute exclusion criterion. 1
• In patients with prior GVHD, the disease must have completely resolved and all systemic immunosuppression must be discontinued before CAR-T eligibility. 1
• Recent donor lymphocyte infusion requires at least 6 weeks between DLI and CAR-T infusion. 1
• Any systemic immunosuppressive treatment is a relative contraindication as it may impair CAR-T efficacy; intermittent topical, inhaled, or intranasal corticosteroids are permitted. 1

Central Nervous System Disease

• Active CNS pathology is a relative contraindication requiring careful risk-benefit assessment, particularly for products associated with immune effector cell-associated neurotoxicity syndrome (ICANS). 1
• Consideration must be given to whether immune activation or tumor flare could compromise vital organ function (airway or CNS). 1
• Controlled secondary CNS lymphoma was permitted in some trials (e.g., Transcend-world), but active CNS involvement was excluded in pivotal studies (ZUMA-1, Juliet, ELIANA, ZUMA-2, KarMMa). 1

Organ Function and Comorbidities

While specific organ dysfunction thresholds vary by manufacturer and product:

• Ability to undergo safe leukapheresis is essential, which can be limiting in infants and small children due to inability to collect sufficient cells. 1
• An absolute lymphocyte count threshold of 0.2 × 10⁹/L is generally recommended for leukapheresis, though emerging evidence supports collection in patients with lower ALC. 1
• Patients must be hemodynamically stable and able to tolerate fluid shifts during leukapheresis. 1

Other Contraindications

• Active malignancy requiring treatment (other than non-melanoma skin cancer or carcinoma in situ) requires careful risk-benefit consideration. 1
• High tumor burden in B-ALL and large B-cell lymphoma is a risk factor for treatment failure and greater toxicity, requiring individualized risk-benefit assessment. 1
• Pregnancy and lactation are contraindications (standard for cellular therapies, though not explicitly detailed in these guidelines).
• Hypersensitivity to product components would preclude therapy per standard pharmaceutical practice.

Important Caveats

Age is NOT a contraindication: The EBMT/EHA guidelines explicitly state no age limit should be applied, with decisions based on physical condition rather than chronological age; real-world data show 5.9% of B-ALL patients were <3 years old and 53.5% of NHL patients were >65 years old with comparable response rates. 1

Prior allogeneic transplant is NOT a contraindication when patients are off immunosuppression, though it may increase toxicity risk in ALL. 1

Prior targeted therapy (bispecific antibodies, prior CAR-T) is NOT a contraindication, but antigen-negative escape should be excluded at relapse before proceeding. 1