Table 2 The recognition and clinical management of CRS in CAR T-cell treatment for B-NHL

From: The model of cytokine release syndrome in CAR T-cell treatment for B-cell non-Hodgkin lymphoma

 

CARTOX grading and management

CRS grading and management for B-NHL

 

CRS

L-CRS

S-CRS

Occurrence time

Day 1–14

Day 1–10

Day 2–14

Grading

Grade 1: (1) Temperature ≥ 38 °C. (2) Grade 1 organ toxicity.

Low-risk: (1) Diameter max < 10 cm. (2) No risk of tumour compression.

Grade 1: Consistent with CARTOX.

Grade 2: (1) Hypotension responds to IV fluids or low-dose vasopressors. (2) Hypoxia requiring FiO2 < 40% (3) Grade 2 organ toxicity.

 

Grade 2: Consistent with CARTOX.

Grade 3: (1) Hypotension needing high-dose or multiple vasopressor. (2) Hypoxia requiring FiO2 ≥ 40%. (3) Grade 3 organ toxicity or grade 4 transaminitis.

High-risk: (1) Diameter max ≥ 10 cm. (2) Dysfunction of vital organs, due to tumour compression. (3) Prospective life-threatening caused by tumour swelling. (4) Involvement of gastrointestinal tract with risks of bleeding and perforation.

Grade 3: Consistent with CARTOX.

Grade 4: (1) Life-threatening hypotension. (2) Needing ventilator support. (3) Grade 4 organ toxicity (excluding transaminitis).

 

Grade 4: Consistent with CARTOX.

Management

Grade 1: (1) Antipyretics for the treatment of fever. (2) Maintenance intravenous fluids for hydration. (3) Management of constitutional symptoms and organ toxicities according to standard guidelines. (4) Consider tocilizumab or siltuximab for persistent and refractory fever. (5) Empiric antibiotic therapy if neutropenic.

Low-risk: Continuous clinical observation and supportive care as per standard guidelines.

Grade 1: (1) Anti-TNF-α agents as recommended for persistent and refractory fever. (2) Other management as consistent with CARTOX.

Grade 2: (1) IV fluid bolus and supplemental oxygen. (2) Tocilizumab or siltuximab ± corticosteroids and supportive care, as recommended for the management of hypotension. (3) Manage fever and constitutional symptoms as in grade 1.

 

Grade 2: (1) Anti-IL-6 therapy ± anti-TNF-α agents as recommended. (2) Other managements are consistent with CARTOX.

Grade 3: (1) IV fluid boluses and vasopressors as needed. (2) Transfer to ICU, and supplemental oxygen as needed. (3) Manage fever and constitutional symptoms as in grade 1. (4) Tocilizumab or siltuximab plus corticosteroids and supportive care, as recommended. (5) Symptomatic management of organ toxicities as per standard guidelines.

High-risk: (1) Continuous clinical observation and supportive care without adjacent organ compression symptoms. (2) Anti-TNF-α agents as needed in the presence of compression symptoms. (3) Local intervention (tracheotomy, drainage of serous effusion) as needed if clinically necessary. (4) Gut purge as recommended for large abdominal tumour lesions and gastrointestinal tract masses. (5) The prophylactic use of anti-TNF-α agents is considered.

Grade 3: (1) Anti-TNF-α agents as recommended if accompanied by L-CRS. (2) Plasma exchange as recommended. (3) Other managements are consistent with CARTOX.

Grade 4: (1) IV fluids, anti-IL-6 therapy, vasopressors and methylprednisolone as recommended. (2) Mechanical ventilation. (3) Manage fever and constitutional symptoms as in grade 1. (4) Tocilizumab or siltuximab plus corticosteroids and supportive care, as recommended. (5) Symptomatic management of organ toxicities as per standard guidelines.

Grade 4: (1) Cyclophosphamide as required. (2) Other management as in grade 3.

  1. CARTOX CAR T-cell-therapy-associated toxicity, CRS cytokine release syndrome, B-NHL B-cell non-Hodgkin lymphoma, CAR chimeric antigen receptor, L-CRS local cytokine release syndrome, S-CRS systemic cytokine release syndrome, TNF-α tumour necrosis factor-α, IL-6 interleukin-6, ICU intensive care unit, IV intravenous injection
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